Function of c-Myc during early development

POLM-IOMEOTIC IS A TARGET OF ENGRAILED REGULATION IN DROSOPHILA. ,SERRANO Nuria; MASCHAT Florence Institut Jacques Monod, 2, pl. fuss& 75251 Paris Cedex 05, France In Drosophila, Engrailed is a nuclear regulatory homeoprotein (DESPLAN C., THEIS I., et O’FARRELL P. H. (1985). Nature, 318, 630-635) with essential roles in embryonic segmentation and in normal development of posterior compartments (KOIUW~G T. (1981). Dev. Biol., 86, 363-372; POOLE S. J., KAUVAR L. M., DREES B. et KORNBERG T. (1985). Cell, 40,37-43; VINCENT J. P. et O’FARRELL P. H. (1942). Cell, 68,923-931). One of its regulatory targets appears to be polykomeotic, a Polycomb group gene. Engrailed protein binds to the site of the polykomeotic locus (polytene region 2D) and to sites upstream of each of the two polykomeotic transcription units. Engrailed binding sites identified in vitro gire also specifically immunoprecipitated in viuo from intact embryonic nuclei where DNA-protein interactions were stabilized by UV crosslinking. During embryogenesis, pofyhonleotic dependence on engrailed function is observed at germ-band elongation when engrailed and polykomeotic are expressed in similar patterns.. These results, together with previous findings showing that the regulation of engraifed expression involves polykomeofic function (DURA J. M. et INGHAM I’. H. (1988). Development, 103, 733-741; SMOUSE D., GOODMAN C. S., MAHOWALD PERRIMON N. (1988). Genes Dev., 2, 830-842) suggest

regulatory

relationships

between

these

two

A. 1’. et cross-

genes.

FUNGION

LEMAITRE lean-Marc, et MECHALI Marcel lnstitui

LBDE,

BP 53 X. 38041

(I) IBMCG,

(2) IGBMC,

CNRS

UPR

In order to establish the distribution pattern of the different RARs in birds, especially during skin morphogenesis, the cDNAs encoding three RARa isoforms (a 1, a’&1 and a2-2), the RARy2, as well as a part of the sequence of a RARP, have been isolated from an 8.5&y chick embryo skin library. While the A! and the B-F domains of the RARa are highly conserved across species, the chick A2-1 and A2-2 domains display uncommon features. Likewise, the A2, B, E, and F domains of the chick RARy show several differences, in particular the F domain is about one-half the length of those of other species. Our results show that the three RAR genes display specific patterns of expression during chick skin development. The RARa and y transcripts are present in both the dermal and epidermal components duricg the first stages of feather formation, and are subsequently restricted to th& epidermal cells The RARfl transcriptr; are present in the dermal and e&&rmal cells up to the beginning of the feather outgrowth. By comparison, during the normal development of mouse skin (WALLET, J. and DHOUAILLW. (1994),1. ~nvzsr. brm., 103. I 16-1~11, the RARa gene is only transientiy espressed tid the RA RP transcripts are never detected. ifhe RARv gene, which exhibits a similar pattern of expression in both chickand mouse skin, is likely to play a similar role during the development of this organ in the different classes di vertebrates.

Robs

high

level

of c-Myc

in the first

embryonic.

nuclei, which returns to a som-atie cell:like level only-at the end of the blastulation period. During early developtienl, when the entire embryonic genome is transcriptionaIly inactive, c-Myc does not exhibit a DNA binding activity in association with Max. These peculiar aspects of c-Myc behavior suggesr :I function that is linked to the rapid DNA replication cycle!. occurring during the early cycles rather than a fuilctiutt involving transcriptional activity.

{C) IBMCG,

F

BOCQUET St@phane, BUCKLE

]acques Monad, LinitC d’Embryolagie Mol&u!air~.. 2, place Jussieu 75251 PARIS Czdex 0.5

an exceptionally

wZLEKBcn&

Grenoble,

EARLY DEVELOPMENT

The proto-oncogene c-myc has been implicated ill several different cellular mechanisms such as proliferation, differentiation and apoptosis. At the molecular level, c-Myc is involved in transcriptional activation. We observed unusual features of c-Myc, specific to the early embryonic development in Xenopus laevis, a period characterized by generalized transcriptional quiescence and rapid bi-phasic cell. cycles. Two c-Myc complexes are present in large amounts in the oocyte and both are localized in th? cytoplasm. A 15 S complex contains ~64 c-Myc and a 17.4 Scomplex contains ~61 c-Myc. Fertilization trigge.rs the selective and total entry of p64 c-Myc info the nucleus. This translocation occurs in a non-progressive manner and is complete by the first cell cycles. This phenomenon results in

CIIAHAC1’EKISATION OF dINAs ISNCODING THlt: TBREI! CHICK RETINOIC ACII) RECEPTOR, a, p AND y , AND THEIR EXPRESSION IWRING CHICK SKIN DEVELOPMENT MICHAILLE Jean-Jacaues (11, BLANCHET Sandrine (11, KANZLER Ben&t (l), GARNIER Jean-Marie (2), DHOUAILLY Danidle (1) 6520, INSERT U184, BP 163, 67404, Illkirch, F

OF C-MYC DURING

HOMEOBOX

GENES

AND

MOUSE

SKIN

RECIONALIZATION (11, VIALLEI‘

BONCINELLl Danielic(l)

Edoardo IJDE.

Jean P.( 1). LL! MOLJELLIC

(3), DUBOIJLE

Ill’ 53X. 3804i

Denis

Hcr>c

(11

(*~),DHOUAI~;[,)’

( ;relrc~hlt~ (‘(‘(It. r. Frmr’c’

(2) lJRA CNRS i 148. 25 rw du Dr ROILX. 75724 I'crri.r CP&.T. I, (3) I.,lilulo Scir~rliJw N.S. R@wle, Vitr Ol~qcrti~ftr60, 201.12 Mihtfi. i (4) %ooloyie ef Binlo,@ Aaitncife, 30 qnai I;. A~r/rmri. I ?/ I C;mr’re i. 5 The expression or six genes belonging lo I\VO d~t’l‘ercrn homeobox gcire families was studied during skin morphogenesls 01 Ihe mouse embry<,. Thi llrst family include the f&I and 01x2 genes, both rclatcd $0 the c~f/i&nlj,.ir Drosoplriln gem, while [he second rvas represented by 10t1r member ol rhr: Antermrtppedicz class HOX genes Hoxdf and three FIoxd genes fffo.rd~, 14; i and dZ3j. In sifrc hybridizations

with 35S labeled antisense

RNA

probes ‘q.ere

performed on head scnul frontonasal sccti 81 differcnlial spalio-lempc?ral paltem along the cephalu-caudal ~Y,S in I?~$-&! embryo. the O/.r2 gene expression is limited 10 lhe nasal epilhcllum ltnd iis associated giands, while the O&I transcnpis arc prescnf b<)ih in. na!& ;~n{: facial integument, including hair vtbrissa follicles. The I-l~.wK and-rtq,o ,,I &C Hox~~genes ~Noxd9 and d/l) were respcclively expressed in the dorsat .rnd catil skin, b) 14.5 da),s OCgestalion Furtherml>rc, the Hr~xr1l.I ~rans~r!!,t~ appear only 2 days aflcr bulb and are rcstrlclcd Lo the h;m malox of chr:c;:u&l @age hair follt&s Taken together. these vbservafions slrenglheN !hl: hypothesis that different-home&box gene famllies spcclfy the rcg~o& itfcnrq oI the skin in the cephahc and body ccg~~,ns