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Sensing self-motion: visual and vestibular mechanisms share the same frame of reference
TINS - September I984
303
Sensing self-motion: visual and vestibular mechanisms share the same frame of reference SeFmotion is monitored by two systems: the vestibular system, which senses head rotation through the semicircular canals, and the visual system, which senses slippage of the image of the world on the retina Recordings in the central visual pathways of lateral-eyed animals have revealed that the two systems organize directional irlformation in remarkably similar ways. Thus, some neurons are tuned to respond best to exactly thosepatterns of retinal image motion that would be evoked by head rotations that maximally excite particular semicircular canals. In order to maintain clear vision, the images on the retina must remain reasonably stable. Head movements pose a serious threat to this stability but are generally dealt with successfully by counter-rotating the eyes. Most ofthe information that the brain uses to sense selfmotion and to generate these cornpen satory eye movements comes from two sources. There are inertial receptors em bedded in the base of the skull which act like angular speedometers, sensing the rotation of the head directly, and initiating compensation through the vestibuloocular reflex (VOR). This system works well at high frequencies but less well at low ones, when the resulting disturbance of gaze brings a second set of receptors into play, visual receptors, which sense the slipping of the retinal image and supplement the compensatory eye movements through a tracking mechanism called the optokinetic reflex (OKR). Thus, the information used to stabilize gaze in space comes from two sensory systems that signal quite different aspects of self-motion, yet ultimately influence the same set of eye muscles in a highly complementary fashion. There are six semicircular canals and each is a fluid-filled, circular tube partitioned by a membrane containing receptor hair cells. Due to the inertia of the fluid, rotations of the head in the response plane of a canal cause its membrane to bulge; depending on the direction of the rotation, this increases or decreases the activity generated by the hair cells. In this way, each canal senses rotations about a particular axis that depends on the canal’s orientation in the skull, and constitutes a polarized, one-dimensional receptor. Throughout the vertebrates, from cartilaginous fishes to primates, the general arrangement of the canals is remarkably uniform, with three on each side of the skull, arranged at right angles to one another: two vertical (anterior and pos terior) and one horizontal. Fig 1 shows the approximate disposition of the canals
in man; note particularly that the vertical canals are oriented 45’ to the parasagittal plane. Each anterior canal is best excited by rotating the head forwards and towards the side of the canal in question; the arrow in Fig 1, for example, indicates the rotation that best excites the left anterior canal. Each posterior canal is maximally excited by rotating the head backwards and towards the side of the canal in question. For the horizontal canals, the preferred rotation is about the vertical axis, excitation again occurring with motion towards the side of the canal
@ 1984. Elscvier
under consideration. Note that the canals function in pairs: each canal is in parallel with one on the opposite side which senses motion about the same preferred rotational axis but with opposite polarity. Clearly, the two horizontal canals work together as a unit, and each anterior canal is paired with the posterior canal on the other side. Thus, in accordance with their orientations in the skull, the three pairs of canals effectively decompose any head rotation into three independent compo nents. Clearly, the VOR must resolve these inputs into appropriately directed compensatory eye movements. Although under no similar physical constraint there is increasing evidence that in some animals at least, the visual input to the OKR is organized in these same vestibular co ordinates. The notion that the visual and vestibular inputs involved in stabilizing gaze might share the same frame of reference came from the realization that both monitor self-motion’. The OKR attempts to make up for shortcomings in the VOR and it is instructive to consider the potential visual consequences of head rotations that maximally excite particular canals. Fig 2 attempts to do this for the rabbit’s left eye, for rotations that optimally excite each of
Science
Publications
B.V.. Amsterdam
0378 - 5912/84/SO2.00
TINS - September 1984
304 the anterior canals. The visual conse quences of the rotations are indicated by optic flow lines on the surface of a sphere centered on the animal’s left eye. These lines indicate the pattern of movement that would be seen by the left eye viewing a stationary world if the VOR failed to compensate fully for the head rotation. (For geometrical convenience, it is assumed) that the head actually rotates about the left eye.) As depicted in Fig 2, the left anterior canal is almost perpendicular to the page and would be maximally excited by tilting the animal’s head to wards the reader, i.e. forwards and to the animal’s left During such rotation, assuming a poor VOR the animal’s left eye would see the world rotate counter-clockwise about an axis some 45” into the temporal visual field (see the continuous optic flow lines centered around the view tine through A in Fig 2). Similarly, the right anterior canal is depicted roughly in the
plane of the page, and would be optimally excited by rotating the page counter-clockwise Assuming a lessthanadequate VOR, the animal’s left eye would then see its visual world rotate counter-clockwise about an axis 45” into the nasal visual field (dashed flow lines centered around the view line through C in Fig 2). Simpson and his colleagues have re corded from neurons in the rabbit’s mid brain that are thought to participate in the OKR7-g. These neurons responded to moving visual patterns and showed strong preferences for movements that were directed along the optic flow lines for the two anterior canals. Thus, neurons whose receptive fields were in the upper part of the central visual field (above location B in Fig 2) responded preferentially to movements that were either upward with a slight posterior component (cf. flow lines for the left anterior canal), or down ward with a slight posterior component
(cf. flow lines for the right anterior canal). Further forward in the visual field, dramatic differences were evident in directional preferences, even within the individual receptive fields, exactly in accordance with the optic flow lines for the right anterior canal. For example, at location ‘a’ in Fig 2 neurons would prefer upward movement with a slight posterior component, while at location ‘b’ the same neurons would prefer downward movement with a slight posterior component. Yet other neurons responded selectively in accordance with the flow lines for the horizontal canals (not shown). The clear suggestion here is that the neurons encoding the visual input to the OKR respond preferentially to rotations of the visual world about axes that coincide with the axes of head rotation that preferentially excite the semicircular canals. Presumably, this shared frame of reference evolved to facilitate the orderly
Fig. 2. Theapproximatedispositicm ofthesemicircuiarcanals in the rabbit, and thepattem of visualshinulatibn that wouldresultfmm rotatikg the headaround axes that maximal1.v excite each of the anterior canals (orthographic projection): opticjlow linesfor the left anterior canal are shown in conrinuous line and those for the right anterior canal in dashed line The optic axis of the rabbit’s eye(B) is of course, notjixed but varies with eyemovements;for the purpose of the present exposition it k assumed to be 90” to the long axis of the head bisecting the angle between theprefeerred rotational axesfor the two anterior canals Optic/low lines are separated by IS”. See text for discussion (After Simpson’.)
TINS - September
1984
summation of visual and vestibular information. There is some evidence to suggest that the visual input mediating the OKR in another lateraLeyed animal, the bird may also be organized around a vestibular coordinate system ‘O-Iz. However, it is not yet clear if the phenomenon is widespread The results of similar recordings in the cat”lJ, a frontal-eyed animal, have been taken to indicate somewhat different organ izational principles in this species, but the analytical technique used in these studies may have obscured any preference for the canal response planed. One of the interesting issues that must be resolved in the future concerns the effects of eye movements. The problem here is that the visual system operates in retinocentric coordin ates that move with the eyes, while the vestibular system operates in head-centered coordinates. Consider, for instance, what would happen if the rabbit in Fig. 2 were to displace its left eye towards the temporal field Those regions of the retina
305
previously coding events at location C, for example, would now be concerned with events nearer to location B, and those visual neurons whose directional responses were in accord with the flow lines at location C would clearly not be in register with the flow lines at the new location, Acknowledgements The author thanks John Shaw for writing the computerprogramusedto draw the otthographicprojectionin Fig. 2.
IO II 12
Reading
list
I Simpson. J. 1.. Soodak. R E. and Hess R ( 1979) in Progress in Brain Research (Granit R and Pompeiano. 0.. eds). Vol. 50. pp. 715724. Elsevier/North Holland, Amsterdam 2 Leonard C. S.. Simpson. J. I. and Soodak. R E. (1981) Neurosci Absrr. 7. 24 3 Simpson. J. 1. (I 984) Annu Rel: Neurosci 7. 1341 4 Simpson. .I. 1.. Graf. W. and Leonard C. ( I98 1) in Progress in Oculomoror Research Dev. Neurosci Vol. 12. (Fuchs, A. F. and Becker.
Normal development of heart and thymus depends on neural crest derivatives As the source of the vast majority of the ganglion cells of the vertebrate peripheral nervous system‘, the neural crest has recently been thrust into considerable prominence Howeven this embryonic structure also makesan extensive contribution to mesenchymal (‘mesectodermal> components in the face and neckz.3.4.s.6. Two recentpublicah’ons7.ahighlight embryological links betweenthe circulatory, immune and nervous systems, thus helping to provide a rational basisfor the recognih’on of certain clinical syndromes involving clusters of developmental defects. The articles from IL4 Kirby’s laboratory in Augusta Georgia, describe the effects on the development of the heart and thymus respectively, of bilateral ablation of short, defined stretchesof neural crest (before migration has begun) at the posterior rhombencephalic level of chick embryos. Examined 7-15 days after the operation, the subjectsdisplayed marked abnormalities of both organs. Over 90% of the hearts possessedaorticopulmonary septal malformations, featuring common ventricular outflow channels or transposition of the great vessels,and thymus tissue was much reduced or absent in all experimental embryos. The extent of the anomaliesobservedis far from reflecting the quantitative contribution of neural crest to the structure either’ of the heart or the thymus. Construction of quail-chick chimaeras has demonstrated that in the thymus the participation of crest-derived cells is limited to connective tissues of the interlobular spaces and of the blood vessels9.The major involvement of neural crest mesec
9
toderm in thymus formation appearsto be indirect, via interaction with endoderm from pharyngeal pouches III and IV, which can then differentiate and sustain thymopoiesis’O. As for cardiac development. although mesenchymeof the aortic archeshasbeen shown to derive from neural cresP, the latter was not thought to contribute to the heart itself. However, Kirby etal, alsoby meansof chimaeric techniques, found the developingtruncal septumto be colonized by a significant number of crest-derived cells, apparently distinct from cardiac ganglioblasts”, which possibly arrive in this location via a secondary migration of the sixth aortic arch mesenchyme. The exact part they play in truncal septation remains to be determined, but it seems clear from theseexperiments that cells of neural crest origin with mesectodermal potentialities are required, directly or indirectly, for normal aorticopulmonary septumdevelopment- just asthey are for the constitution of a normal thymus. Failure of the normal biological com0
1984. Elsewer
13 14
W.. eds). pp. 475-484. ElseviedNorth Holland Amsterdam Simpson. J. I. and Soodak R E. (1978) Neurosci Absrr. 4. 645 Simpson. J. I.. Soodak. R E. and Leonard C. S. (I 982) Neurosci Abstr. 8. 407 Collewijn. H. (I 975) Brain Res. 100.489-508 Collewijn. H. (1975) J. Neurobiol 6. 3-22 Oyster. C. W.. Takahashi. E. and Collewijn H. (1972) Vision Res. 12. 183-193 Bums. S. and Wallman J. ( 198 1) Exp. Brain Res 42. 171-180 Morgan. B. and Frost. B. J. ( 198 1) Exp. Brain Rex 42. 181-188 Wallman. J.. McKenna 0. C.. Bums. S. and Velez. J. ( I98 1 ) in Progress in Oculomoror Research Dev. Neurosci Vol. I2 (Fuchs A. F. and Becker. W.. eds), pp. 435-442. Elsevied North Holland Amsterdam Grasse. K L. and Cynader. M. S. (1382) J. NeurophvsioL 48. 490-504 Grasse. K L and Cynader. M. S. (1984) J. NeurophysioL 5 1. 276-293
F. A. MILES Laboratov of Sensotimoror Research National Eye Institute, National Institutes of Health. Bethesda, MD 20205, USA.
petence of neural crest at the appropriate axial level, whether resulting from insufficiency of crest cell formation. migration, multiplication, differentiation or interaction, would thus be expected to have more or lessextreme effects on the development of the heart and thymus. The effects would also be expected to apply to other derivatives of that particular region of the neuraxis, including the peripheral ganglia This was indeed the case in Kirby’s experiments. where the consequencesof the total ablation of the neural folds over somitesl-5 included anomalousdevelop ment of thyroids and parathyroids, and reduction of cardiac ganglia Although they were not examined in this study, deficiencies presumably occurred also in the intrinsic innervation of the gut which originates in great part from the posterior rhombencephalic level ofthe neural fold’. Extirpation of neural crest obviously constitutesa drastic teratological situation Nevertheless. such surgically provoked clustersof developmental defects do have their equivalents in human embryology, for example in the syndromes of Di George and Robin, in which congenital absenceor hypoplasia of the thymus and parathyroids is accompanied by malformationsof the largevasculartrunks derived from the aortic arches.That thesedisorders are the result of an effective deletion of rhombencephalic neural crest has, in fact, already been cogently argued12.In a considerable number of other human birth disorders,facial, ocular, dental, glandular and neurological aberrations are asso ciated in a manner that is eloquently suggestive of a common denominator at Scwnce Pubhcattons
B.V.
Amsterdam
0378 - 5912/84/502.00
303
Sensing self-motion: visual and vestibular mechanisms share the same frame of reference SeFmotion is monitored by two systems: the vestibular system, which senses head rotation through the semicircular canals, and the visual system, which senses slippage of the image of the world on the retina Recordings in the central visual pathways of lateral-eyed animals have revealed that the two systems organize directional irlformation in remarkably similar ways. Thus, some neurons are tuned to respond best to exactly thosepatterns of retinal image motion that would be evoked by head rotations that maximally excite particular semicircular canals. In order to maintain clear vision, the images on the retina must remain reasonably stable. Head movements pose a serious threat to this stability but are generally dealt with successfully by counter-rotating the eyes. Most ofthe information that the brain uses to sense selfmotion and to generate these cornpen satory eye movements comes from two sources. There are inertial receptors em bedded in the base of the skull which act like angular speedometers, sensing the rotation of the head directly, and initiating compensation through the vestibuloocular reflex (VOR). This system works well at high frequencies but less well at low ones, when the resulting disturbance of gaze brings a second set of receptors into play, visual receptors, which sense the slipping of the retinal image and supplement the compensatory eye movements through a tracking mechanism called the optokinetic reflex (OKR). Thus, the information used to stabilize gaze in space comes from two sensory systems that signal quite different aspects of self-motion, yet ultimately influence the same set of eye muscles in a highly complementary fashion. There are six semicircular canals and each is a fluid-filled, circular tube partitioned by a membrane containing receptor hair cells. Due to the inertia of the fluid, rotations of the head in the response plane of a canal cause its membrane to bulge; depending on the direction of the rotation, this increases or decreases the activity generated by the hair cells. In this way, each canal senses rotations about a particular axis that depends on the canal’s orientation in the skull, and constitutes a polarized, one-dimensional receptor. Throughout the vertebrates, from cartilaginous fishes to primates, the general arrangement of the canals is remarkably uniform, with three on each side of the skull, arranged at right angles to one another: two vertical (anterior and pos terior) and one horizontal. Fig 1 shows the approximate disposition of the canals
in man; note particularly that the vertical canals are oriented 45’ to the parasagittal plane. Each anterior canal is best excited by rotating the head forwards and towards the side of the canal in question; the arrow in Fig 1, for example, indicates the rotation that best excites the left anterior canal. Each posterior canal is maximally excited by rotating the head backwards and towards the side of the canal in question. For the horizontal canals, the preferred rotation is about the vertical axis, excitation again occurring with motion towards the side of the canal
@ 1984. Elscvier
under consideration. Note that the canals function in pairs: each canal is in parallel with one on the opposite side which senses motion about the same preferred rotational axis but with opposite polarity. Clearly, the two horizontal canals work together as a unit, and each anterior canal is paired with the posterior canal on the other side. Thus, in accordance with their orientations in the skull, the three pairs of canals effectively decompose any head rotation into three independent compo nents. Clearly, the VOR must resolve these inputs into appropriately directed compensatory eye movements. Although under no similar physical constraint there is increasing evidence that in some animals at least, the visual input to the OKR is organized in these same vestibular co ordinates. The notion that the visual and vestibular inputs involved in stabilizing gaze might share the same frame of reference came from the realization that both monitor self-motion’. The OKR attempts to make up for shortcomings in the VOR and it is instructive to consider the potential visual consequences of head rotations that maximally excite particular canals. Fig 2 attempts to do this for the rabbit’s left eye, for rotations that optimally excite each of
Science
Publications
B.V.. Amsterdam
0378 - 5912/84/SO2.00
TINS - September 1984
304 the anterior canals. The visual conse quences of the rotations are indicated by optic flow lines on the surface of a sphere centered on the animal’s left eye. These lines indicate the pattern of movement that would be seen by the left eye viewing a stationary world if the VOR failed to compensate fully for the head rotation. (For geometrical convenience, it is assumed) that the head actually rotates about the left eye.) As depicted in Fig 2, the left anterior canal is almost perpendicular to the page and would be maximally excited by tilting the animal’s head to wards the reader, i.e. forwards and to the animal’s left During such rotation, assuming a poor VOR the animal’s left eye would see the world rotate counter-clockwise about an axis some 45” into the temporal visual field (see the continuous optic flow lines centered around the view tine through A in Fig 2). Similarly, the right anterior canal is depicted roughly in the
plane of the page, and would be optimally excited by rotating the page counter-clockwise Assuming a lessthanadequate VOR, the animal’s left eye would then see its visual world rotate counter-clockwise about an axis 45” into the nasal visual field (dashed flow lines centered around the view line through C in Fig 2). Simpson and his colleagues have re corded from neurons in the rabbit’s mid brain that are thought to participate in the OKR7-g. These neurons responded to moving visual patterns and showed strong preferences for movements that were directed along the optic flow lines for the two anterior canals. Thus, neurons whose receptive fields were in the upper part of the central visual field (above location B in Fig 2) responded preferentially to movements that were either upward with a slight posterior component (cf. flow lines for the left anterior canal), or down ward with a slight posterior component
(cf. flow lines for the right anterior canal). Further forward in the visual field, dramatic differences were evident in directional preferences, even within the individual receptive fields, exactly in accordance with the optic flow lines for the right anterior canal. For example, at location ‘a’ in Fig 2 neurons would prefer upward movement with a slight posterior component, while at location ‘b’ the same neurons would prefer downward movement with a slight posterior component. Yet other neurons responded selectively in accordance with the flow lines for the horizontal canals (not shown). The clear suggestion here is that the neurons encoding the visual input to the OKR respond preferentially to rotations of the visual world about axes that coincide with the axes of head rotation that preferentially excite the semicircular canals. Presumably, this shared frame of reference evolved to facilitate the orderly
Fig. 2. Theapproximatedispositicm ofthesemicircuiarcanals in the rabbit, and thepattem of visualshinulatibn that wouldresultfmm rotatikg the headaround axes that maximal1.v excite each of the anterior canals (orthographic projection): opticjlow linesfor the left anterior canal are shown in conrinuous line and those for the right anterior canal in dashed line The optic axis of the rabbit’s eye(B) is of course, notjixed but varies with eyemovements;for the purpose of the present exposition it k assumed to be 90” to the long axis of the head bisecting the angle between theprefeerred rotational axesfor the two anterior canals Optic/low lines are separated by IS”. See text for discussion (After Simpson’.)
TINS - September
1984
summation of visual and vestibular information. There is some evidence to suggest that the visual input mediating the OKR in another lateraLeyed animal, the bird may also be organized around a vestibular coordinate system ‘O-Iz. However, it is not yet clear if the phenomenon is widespread The results of similar recordings in the cat”lJ, a frontal-eyed animal, have been taken to indicate somewhat different organ izational principles in this species, but the analytical technique used in these studies may have obscured any preference for the canal response planed. One of the interesting issues that must be resolved in the future concerns the effects of eye movements. The problem here is that the visual system operates in retinocentric coordin ates that move with the eyes, while the vestibular system operates in head-centered coordinates. Consider, for instance, what would happen if the rabbit in Fig. 2 were to displace its left eye towards the temporal field Those regions of the retina
305
previously coding events at location C, for example, would now be concerned with events nearer to location B, and those visual neurons whose directional responses were in accord with the flow lines at location C would clearly not be in register with the flow lines at the new location, Acknowledgements The author thanks John Shaw for writing the computerprogramusedto draw the otthographicprojectionin Fig. 2.
IO II 12
Reading
list
I Simpson. J. 1.. Soodak. R E. and Hess R ( 1979) in Progress in Brain Research (Granit R and Pompeiano. 0.. eds). Vol. 50. pp. 715724. Elsevier/North Holland, Amsterdam 2 Leonard C. S.. Simpson. J. I. and Soodak. R E. (1981) Neurosci Absrr. 7. 24 3 Simpson. J. 1. (I 984) Annu Rel: Neurosci 7. 1341 4 Simpson. .I. 1.. Graf. W. and Leonard C. ( I98 1) in Progress in Oculomoror Research Dev. Neurosci Vol. 12. (Fuchs, A. F. and Becker.
Normal development of heart and thymus depends on neural crest derivatives As the source of the vast majority of the ganglion cells of the vertebrate peripheral nervous system‘, the neural crest has recently been thrust into considerable prominence Howeven this embryonic structure also makesan extensive contribution to mesenchymal (‘mesectodermal> components in the face and neckz.3.4.s.6. Two recentpublicah’ons7.ahighlight embryological links betweenthe circulatory, immune and nervous systems, thus helping to provide a rational basisfor the recognih’on of certain clinical syndromes involving clusters of developmental defects. The articles from IL4 Kirby’s laboratory in Augusta Georgia, describe the effects on the development of the heart and thymus respectively, of bilateral ablation of short, defined stretchesof neural crest (before migration has begun) at the posterior rhombencephalic level of chick embryos. Examined 7-15 days after the operation, the subjectsdisplayed marked abnormalities of both organs. Over 90% of the hearts possessedaorticopulmonary septal malformations, featuring common ventricular outflow channels or transposition of the great vessels,and thymus tissue was much reduced or absent in all experimental embryos. The extent of the anomaliesobservedis far from reflecting the quantitative contribution of neural crest to the structure either’ of the heart or the thymus. Construction of quail-chick chimaeras has demonstrated that in the thymus the participation of crest-derived cells is limited to connective tissues of the interlobular spaces and of the blood vessels9.The major involvement of neural crest mesec
9
toderm in thymus formation appearsto be indirect, via interaction with endoderm from pharyngeal pouches III and IV, which can then differentiate and sustain thymopoiesis’O. As for cardiac development. although mesenchymeof the aortic archeshasbeen shown to derive from neural cresP, the latter was not thought to contribute to the heart itself. However, Kirby etal, alsoby meansof chimaeric techniques, found the developingtruncal septumto be colonized by a significant number of crest-derived cells, apparently distinct from cardiac ganglioblasts”, which possibly arrive in this location via a secondary migration of the sixth aortic arch mesenchyme. The exact part they play in truncal septation remains to be determined, but it seems clear from theseexperiments that cells of neural crest origin with mesectodermal potentialities are required, directly or indirectly, for normal aorticopulmonary septumdevelopment- just asthey are for the constitution of a normal thymus. Failure of the normal biological com0
1984. Elsewer
13 14
W.. eds). pp. 475-484. ElseviedNorth Holland Amsterdam Simpson. J. I. and Soodak R E. (1978) Neurosci Absrr. 4. 645 Simpson. J. I.. Soodak. R E. and Leonard C. S. (I 982) Neurosci Abstr. 8. 407 Collewijn. H. (I 975) Brain Res. 100.489-508 Collewijn. H. (1975) J. Neurobiol 6. 3-22 Oyster. C. W.. Takahashi. E. and Collewijn H. (1972) Vision Res. 12. 183-193 Bums. S. and Wallman J. ( 198 1) Exp. Brain Res 42. 171-180 Morgan. B. and Frost. B. J. ( 198 1) Exp. Brain Rex 42. 181-188 Wallman. J.. McKenna 0. C.. Bums. S. and Velez. J. ( I98 1 ) in Progress in Oculomoror Research Dev. Neurosci Vol. I2 (Fuchs A. F. and Becker. W.. eds), pp. 435-442. Elsevied North Holland Amsterdam Grasse. K L. and Cynader. M. S. (1382) J. NeurophvsioL 48. 490-504 Grasse. K L and Cynader. M. S. (1984) J. NeurophysioL 5 1. 276-293
F. A. MILES Laboratov of Sensotimoror Research National Eye Institute, National Institutes of Health. Bethesda, MD 20205, USA.
petence of neural crest at the appropriate axial level, whether resulting from insufficiency of crest cell formation. migration, multiplication, differentiation or interaction, would thus be expected to have more or lessextreme effects on the development of the heart and thymus. The effects would also be expected to apply to other derivatives of that particular region of the neuraxis, including the peripheral ganglia This was indeed the case in Kirby’s experiments. where the consequencesof the total ablation of the neural folds over somitesl-5 included anomalousdevelop ment of thyroids and parathyroids, and reduction of cardiac ganglia Although they were not examined in this study, deficiencies presumably occurred also in the intrinsic innervation of the gut which originates in great part from the posterior rhombencephalic level ofthe neural fold’. Extirpation of neural crest obviously constitutesa drastic teratological situation Nevertheless. such surgically provoked clustersof developmental defects do have their equivalents in human embryology, for example in the syndromes of Di George and Robin, in which congenital absenceor hypoplasia of the thymus and parathyroids is accompanied by malformationsof the largevasculartrunks derived from the aortic arches.That thesedisorders are the result of an effective deletion of rhombencephalic neural crest has, in fact, already been cogently argued12.In a considerable number of other human birth disorders,facial, ocular, dental, glandular and neurological aberrations are asso ciated in a manner that is eloquently suggestive of a common denominator at Scwnce Pubhcattons
B.V.
Amsterdam
0378 - 5912/84/502.00