Abstracts - Society for Developmental Biology

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homeodomain (HD) transcription factors like Pax2 that specify the inhibitory GABAergic lineage while suppressing HD
factors like Tlx1/3 that specify the excitatory glutamatergic lineage in the dorsal spinal cord. Utilizing deep sequencing of
chromatin immunoprecipitation (ChIP-seq) and gene expression profiling (RNA-seq) in Ptf1a mutant versus wildtype
neural tubes, we identified Prdm13, a putative chromatin-remodeling zinc finger transcription factor, as a direct
downstream target of Ptf1a for explaining how Ptf1a can suppress gene expression. Prdm13 is lost in Ptf1a domains in the
Ptf1a null mouse. In both gain and loss of function experiments in chick neural tube, Prdm13 phenocopies Ptf1a by
inducing Pax2 + /GABAergic neurons and suppressing the Tlx1/3 + /glutamatergic neurons. This neuronal cell-fate
specification function by Prdm13 requires the zinc finger domains and transcriptional repressor activity. Epistasis
experiments confirm Prdm13 functions downstream of Ptf1a, and Ptf1a requires Prdm13 for its function in neuronal
specification. Furthermore, Prdm13 regulates this neuronal specification through directly repressing transcription of
dI5/dILB lineage genes through DNA binding activity. This activity of Prdm13 acts antagonistically to the bHLH factor
Ascl1, which at this stage directs progenitors to the Tlx1/3 glutamatergic lineage. Our findings demonstrate that Prdm13 is
a novel component of a highly coordinated transcriptional network necessary to mediate the balance of inhibitory versus
excitatory neurons generated in the dorsal neural tube.
Program/Abstract # 439
Sulfatase 1, an extracellular regulator of the motoneuron to oligodendrocyte cell fate choice in the ventral spinal
cord
Touahri, Yacine, toulouse, France; Escalas, Nathalie; Danesin, Cathy; Soula, Cathy (Toulouse, France)
In the developing vertebrate spinal cord, oligodendrocyte precursor cells (OPCs) mainly originate from ventral neural
progenitors of the pMN domain, marked by Olig2 expression. These progenitors first generate motoneurons (MNs) and
switch to an OPC fate after completion of MN generation. We previously evidenced that Sulfatase 1 (Sulf1), a secreted
endosulfatase, is upregulated in ventral neural progenitors immediately prior to OPC specification. Sulf1 is known to
regulate the sulfation state of heparan sulfate proteoglycans (HSPGs), extracellular matrix molecules involved in regulating
various signaling pathways. To assess Sulf1 function in the MN/OPC switch, we recently analyzed OPC development in
mice lacking Sulf1 function. Our results clearly showed that specification of ventral OPCs is severely affected in Sulf1-/-
mutant mice. Indeed, the efficiency of OPC induction is reduced, only few pMN progenitors switch to an OPC fate while
they continue to generate MNs passed the normal timing of the MN/OPC switch. Moreover, using chick spinal cord
explants, we showed that the deficiency in OPC production in Sulf1 loss of function is not a consequence of an early
phenotype but results from the timely regulated expression of Sulf1. Finally, we bring arguments supporting that Sulf1
controls the MN/OPC switch by regulating Shh activity. Our work then establish that Sulf1 is a major component of the
mechanisms that cause neural progenitors of the pMN domain to stop producing neurons and switch to an OPC fate.
Program/Abstract # 440
Removal of Polycomb Repressive Complex 2 makes C. elegans germ cells susceptible to direct conversion into
specific somatic cell types
Patel, Tulsi, Genetics and Development, New York, United States; Tursun, Baris (The Berline Institute for Medical
Systems Biology, Berlin, Germany); Rahe, Dylan; Hobert, Oliver (Columbia University, New York, NY, United States)
How specific cell types can be directly converted into other distinct cell types is a matter of intense investigation with
wide-ranging basic and biomedical implications. We have recently shown that the removal of the histone chaperone LIN-
53 (called Rbbp4 and Rbbp7 in vertebrates) permits ectopically expressed, neuron-type-specific transcription factors
(terminal selectors) to convert C. elegans germ cells directly into specific neuron types. How the LIN-53 protein protects
the germ cell genome from being converted was unclear since histone chaperones like LIN-53 function in a number of
distinct, chromatin-related processes, including nucleosome assembly, remodeling, and various types of gene activation
and repression events. We show here that the function of LIN-53 in the germ cell to neuron conversion process can be
phenocopied by loss of members of the histone 3 lysine 27 (H3K27) methyltransferase complex PRC2. Terminal selectorinduced
germ cell to neuron conversion can not only be observed upon genome-wide loss of H3K27 in PRC2(-) animals,
but also upon genome-wide redistribution of H3K27 in animals which lack the H3K36 methyltransferase MES-4.
Manipulation of the H3K27 status not only permits neuronal terminal selector-dependent conversion of germ cells into
neurons, but also permits hlh-1/MyoD -dependent conversion of germ cells into muscle cells, indicating the PRC2 protects
the germline from the aberrant execution of multiple distinct somatic differentiation programs. Taken together, our findings
demonstrate that the normally multi-step process of development from a germ cell via a zygote to a terminally
differentiated somatic cell type can be shortcut by providing an appropriate terminal selector transcription factor and
manipulating histone methylation patterns.