07-P007 The adaptor protein Btbd6a targets the degradation of an inhibitor to enable neuronal differentiation

S138

MECHANISMS OF DEVELOPMENT

1 2 6 (2 0 0 9) S1 3 7–S 14 3

3

PPARc), enzymes (stearoyl-Coenzyme A desaturase 1, lactate

icine, Taoyuan, Taiwan

dehydrogenase B) and secreted factors (resistin, adipsin). At

Department of Biochemistry, Chang-Gung University College of Med-

e17.5, 30% of upregulated genes were adipocyte related, but these Previous studies have demonstrated that depletion of Gas7

included genes not previously associated directly with adipogen-

impedes neurite outgrowth in primary cultures of Purkinje neu-

esis. These data are therefore being used to uncover genes whose

rons, and that Gas7 promotes neurite outgrowth in PC12 cells.

involvement in adipogenesis is currently unrecognized, and that

To investigate the physiological function of Gas7, we generated

could eventually serve as targets for modulation of fat accumula-

by homologous recombination a Gas7-mutant mouse which pro-

tion. This work provides a first molecular analysis of cutaneous

duced a Gas7 variant protein with an in-frame deletion of amino

adipocyte development insitu, but also raises several new ques-

acid residues 103–120. Only low levels of the Gas7 variant protein

tions: does signalling between hair follicles and surrounding cells

were found in the mutant mice because of a shortened protein

in the lower dermis regulate adipogenesis; do hair follicle mesen-

half-life. In comparison with the wild type, mutant mice had

chymal cells contribute to the adipocyte cell pool; and what inhib-

reduced motor activity and muscle strength which could be

its adipocyte differentiation in the upper dermis?

ascribed to deficits in skeletal muscle fast-twitch fibers, with a much smaller proportion of the IIa/x myofiber subtype found in

doi:10.1016/j.mod.2009.06.289

the soleus. Gross morphological features of the neuromuscular junction including the pattern of axon terminal branches and the shape of AChR clusters in the soleus remained generally unchanged between the wild type and mutant mice, though end-

07-P007

plate average size and nAChR transcription levels rose in the

The adaptor protein Btbd6a targets the degradation of an inhib-

mutant. Gas7 variant protein was localized in the terminal Schw-

itor to enable neuronal differentiation

ann cells and in the presynaptic region of motor axons, a similar

Dorothy F. Sobieszczuk, Alexei Poliakov, David G. Wilkinson

pattern to the wild-type Gas7, but at lower levels. This is the first

National Institute for Medical Research, London, United Kingdom

evidence that Gas7 is expressed not only in central neurons, but also in Schwann cells and output axons of the peripheral nervous system. The results also suggest that Gas7 may control AChR expression or clustering and thus affect muscle strength and motor activity. doi:10.1016/j.mod.2009.06.287

Neurogenesis is regulated by a network of proneural genes that promote neuronal differentiation and inhibitors that maintain progenitor cells. The initiation of neuronal differentiation requires a switch in which proneural gene expression is upregulated from an initial low level. We have uncovered a novel feedback loop mediating such a switch during primary neurogenesis that is mediated by a ubiquitin adaptor protein. We find that the proneural gene neurogenin1 upregulates the expression of a

07-P005 – Withdrawn

BTB-PHR domain gene, btbd6a, which in turn is required for the upregulation of neurogenin1. We show that Btbd6a acts as an adaptor protein for the Cul3 ubiquitin ligase complex, and that it mediates the degradation of a novel inhibitor of neurogenesis,

07-P006

which is widely expressed in the neuroepithelium. This is the first

A new insitu study of the cellular and molecular basis of adipo-

evidence for a role of targeted protein degradation in the initia-

genesis using developing mouse skin

tion of vertebrate neurogenesis.

Kamila

Wojciechowicz1, Claire Higgins2, Angela Christiano2,

Colin Jahoda1

doi:10.1016/j.mod.2009.06.290

1

Durham University, Durham, United Kingdom

2

Columbia University, New York, United States Current information on the cellular and molecular basis of

adipogenesis derives principally from invitro studies on cell lines. As part of a broader investigation into the developmental relationship between hair follicles and subcutaneous fat, we recently showed that C/EPBa labelled preadipocytes are located around hair follicles in the deep dermis of embryonic mouse back skin.

07-P008 Regulation

of

alternative

Ciz1

variant

expression

during

development Erin Greaves1, Dawn Coverley2, Justin Ainscough1 1

University of Leeds, Leeds, United Kingdom

2

University of York, York, United Kingdom

Here we employed laser capture microdissection and whole genome Affymetrix microarray analysis to compare cells from adipo-

Ciz1 (CDKN1A interacting zinc finger protein 1) is a novel

cyte forming and non adipocyte forming dermis. Samples were

nuclear matrix associated DNA replication factor. Originally iden-

taken from prior to C/EBPa labelling of preadipocytes (e17.5)

tified through its interaction with CDKN1A (p21cip1) it has since

through to the emergence of adipocytes with lipid droplets

been associated with an increasingly diverse set of proteins.

(e19.5). Transcriptome analysis of cells from the lower dermis at

Ciz1 is alternatively spliced, and exclusion of specific regions

e19.5 revealed that over 50% of around 500 upregulated genes

influences its sub-nuclear localisation. Whilst variant forms of

have been previously linked with adipogenesis and/or mature

Ciz1 have been linked to disease states, regulation of Ciz1 expres-

adipocyte activity. These included transcription factors (C/EBPa,

sion in development has not been investigated. We have gener-