Stowers Institute for Medical Research
Host: Marty Chalfie
Title: Hox genes and the hindbrain: A story in segments
Abstract: The vertebrate hindbrain is a highly conserved co-ordination center of the CNS where regional diversity and patterning of neurogenesis is achieved through a process of segmentation, giving rise to well-defined regions of the adult brain. The Hox family of transcription factors is coupled to this process and provides a molecular framework for specifying the unique identities of hindbrain segments and developing neurons. Cis-regulatory analyses have provided significant insight and understanding of the gene regulatory networks, transcriptional mechanisms and signaling cascades through which the expression and function of the Hox gene family controls patterning of the hindbrain and craniofacial region in development, disease and evolution. Genomic and biochemical approaches have been used to investigate the roles of epigenetics and changes in chromatin states in regulation of Hox complexes. This framework has enabled us to determine the degree to which the hindbrain regulatory network is conserved during evolution of chordates. Finally, we are using genomic and proteomic approaches in mouse tissues and programmed differentiation of mouse ES cells to identify downstream Hox target genes on a genome-wide basis and to link these loci to the pathways and cellular processes they modulate. This is building a mechanistic understanding of how HOX proteins bind DNA and regulate regional identity.