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Abstracts - Society for Developmental Biology

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102<br />

Cdx1 peaks in the distal colon and Cdx2 in the proximal cecum. Moreover, Cdx1 expression is graded along the cryptvillus<br />

axis, with more abundant protein found in the crypts, which house stem cells, and diminishing towards the<br />

differentiated cells in the villi. Cdx2 is expressed uni<strong>for</strong>mly along this crypt-villusaxis, but is differentially phosphorylated.<br />

The functional consequences and mechanisms of regulation of these different expression domains of the Cdx proteins<br />

remain unknown. Herein, we demonstrate that Cdx2 driven by Cdx1 regulatory elements cannot functionally compensate<br />

<strong>for</strong> loss of endogenous Cdx2. Furthermore, we show evidence that Cdx2 cannot functionally compensate <strong>for</strong> Cdx1 in the<br />

context ofintestinal homeostasis in the distal colon. This study provides novel in vivo evidence that Cdx1 and Cdx2 have<br />

context dependent functional specificity.<br />

Program/Abstract # 310<br />

Cdx and FGF interactions establish a molecular switch <strong>for</strong> posterior nervous system specification<br />

Hayward, Albert; Skromne, Isaac, University of Miami, Coral Gables, FL, United States<br />

During development, neural cells can respond to the same signaling factors in remarkably different ways depending on<br />

their molecular context or competence. What determines a cell’s competence and its specific response to signaling inputs<br />

remains unknown. We have investigated issues of neural competence in a simple binary-decision system: the specification<br />

of caudal neural plate cells to hindbrain or spinal cord fates. Hindbrain and spinal cord specification depend on the<br />

signaling activity of FGFs and the caudally restricted transcriptional activity of Cdx. We have examined how molecular<br />

context, presence or absence of Cdx, allows prospective hindbrain cells (Cdx negative) and prospective spinal cord cells<br />

(Cdx positive) to respond in distinctive ways to FGF signaling by activating particular developmental programs in a cellspecific<br />

fashion. Here we show that a network of FGF and Cdx interactions specify and pattern the spinal cord. Using loss<br />

and gain of function strategies, we show that induction of spinal cord fates requires Cdx independently of FGF. However,<br />

subsequent maintenance of spinalcord fates by Cdx requires FGF activity. Similarly, induction of patterning genes (hox)<br />

expression only requires Cdx, but their maintenance requires Cdx and FGF activities. The maintenance of spinal cord<br />

specification and patterning in<strong>for</strong>mation involves the maintenance of Cdx auto-regulation by FGF. We propose that Cdx<br />

and FGF interactions establish a molecular switch that stabilizes the induction of spinal cord fates and promotes the<br />

patterning of posterior nervous system.<br />

Program/Abstract # 311<br />

Interneuron specification in zebrafish spinal cord<br />

Hilinski, William, SUNY Upstate Medical University, Syracuse, United States; England, Samantha; Jager, Sarah;<br />

Rodriguez-Larrain, Gisella; Lewis, Kate (Syracuse Unviersity, Syracuse, NY, United States)<br />

Most of the neurons in the vertebrate Central Nervous System (CNS) are interneurons and interneurons function in almost<br />

all neuronal circuits and behaviors. However, we still know very little about how specific interneurons with particular<br />

physiological and functional characteristics develop and <strong>for</strong>m functional neuronal circuitry. All of the evidence so far<br />

suggests that the properties of distinct spinal cord interneurons are determined by the transcription factors that the cells<br />

express as they become post-mitotic and start to differentiate. However, in many cases, it is still unclear which<br />

transcription factors specify particular interneuron properties. We also do not know the full complement of transcription<br />

factor sexpressed by any population of spinal interneurons in any vertebrate. To address these critical gaps in our<br />

knowledge we are using and developing several techniques. For example, we are Fluorescence Activated Cell-Sorting<br />

(FACS) and expression profiling specific spinal cord interneuron populations using transgenic zebrafish lines where these<br />

cell types are labeled with fluorescent proteins. This enables us to identify all of the transcriptionfactors expressed by these<br />

different interneuron populations. Furthermore, we are comparing and contrasting expression profiles of interneurons with<br />

similar and different axon trajectories and/or neurotransmitter phenotypes to identify transcriptions factors that are good<br />

candidates <strong>for</strong> specifying these functional properties. We will then test the functions of these transcription factors using<br />

mutant lines, morpholino oligonucleotides, and dominant-negative constructs. One interneuron population that we are<br />

particularly interested in is V0v spinalcord interneurons. These interneurons are located in the ventral spinal cord and are<br />

part of the CNS circuitry that controls locomotion. They can be identified by their expression of the transcription factor<br />

Evx1, which, within the spinal cord, is uniquely expressed by these interneurons. We are currently identifying all of the<br />

transcription factors expressed by V0v interneurons and inparticular we are examining the functions of different<br />

transcription factors inspecifying V0v axonal and neurotransmitter phenotypes.<br />

Program/Abstract # 312<br />

Specific requirement of floor plate Shh in spinal cord development<br />

Kwanha, Yu, UMDNJ-Piscataway Neuroscience and Cell <strong>Biology</strong>, Piscataway, United States; Matise, Michael<br />

(Piscataway, NJ, United States)

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