TY - JOUR
T1 - Lineage-specific regulation of the neural differentiation gene MASH1
AU - Verma-Kurvari, Sunita
AU - Savage, Trisha
AU - Gowan, Katherine
AU - Johnson, Jane E.
N1 - Funding Information:
We gratefully acknowledge B. Yoshida for the Mash1 cosmid, Dr. A. Boulet for the in situ hybridization protocol on vibratome sections, Dr. H. KraÈ mer for the coinjection idea, and Dr. G. Fishell for advice on neuroanatomy. We also thank Drs. K. Zimmerman, G. Fishell, S. Birren, and L. Parada for critical comments on the manuscript. J.E.J. is an Established Investigator of the American Heart Association. This work was funded by NIH RO1-NS32817, Texas Advanced Research Program, and the Kent Waldrep National Paralysis Foundation.
PY - 1996/12/15
Y1 - 1996/12/15
N2 - Mash1 is a transcription factor required during embryogenesis for the development of multiple neural lineages. It is expressed in cted domains at specific stages in the developing central and peripheral nervous systems and in the developing olfactory epithelium. We have investigated the regulation of Mash1 expression during embryogenesis using transgenic mice containing Mash1/lacZ reporter constructs. Cis-acting regulatory elements controlling Mash1 expression in the central nervous system are located within an 8-kb sequence upstream of the Mash1 coding region. This 8-kb sequence does not contain elements directing expression to the peripheral nervous system, olfactory epithelium, or retina. Sequences outside this 8 kb but within 36 kb of the Mash1 locus contain elements responsible for expression in the autonomic division of the peripheral nervous system. However, transgene expression in embryos containing the 36-kb sequence was never detected in the olfactory epithelium and retina. Thus, regulatory elements driving expression in these lineages may be at even greater distances from the Mash1 coding region. These data provide evidence for complex regulation of Mash1 expression in which multiple lineage-specific cis-acting regulatory regions span greater than 36 kb of the Mash1 locus. Further characterization of these regions will facilitate the study of factors that regulate the temporal and spatial expression of Mash1 during development. In addition, the regulatory sequences identified here can direct expression of heterologous genes to developing neural lineages that normally express Mash1, thus providing an important tool for examining the function of candidate regulatory genes in mammalian nervous system development.
AB - Mash1 is a transcription factor required during embryogenesis for the development of multiple neural lineages. It is expressed in cted domains at specific stages in the developing central and peripheral nervous systems and in the developing olfactory epithelium. We have investigated the regulation of Mash1 expression during embryogenesis using transgenic mice containing Mash1/lacZ reporter constructs. Cis-acting regulatory elements controlling Mash1 expression in the central nervous system are located within an 8-kb sequence upstream of the Mash1 coding region. This 8-kb sequence does not contain elements directing expression to the peripheral nervous system, olfactory epithelium, or retina. Sequences outside this 8 kb but within 36 kb of the Mash1 locus contain elements responsible for expression in the autonomic division of the peripheral nervous system. However, transgene expression in embryos containing the 36-kb sequence was never detected in the olfactory epithelium and retina. Thus, regulatory elements driving expression in these lineages may be at even greater distances from the Mash1 coding region. These data provide evidence for complex regulation of Mash1 expression in which multiple lineage-specific cis-acting regulatory regions span greater than 36 kb of the Mash1 locus. Further characterization of these regions will facilitate the study of factors that regulate the temporal and spatial expression of Mash1 during development. In addition, the regulatory sequences identified here can direct expression of heterologous genes to developing neural lineages that normally express Mash1, thus providing an important tool for examining the function of candidate regulatory genes in mammalian nervous system development.
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U2 - 10.1006/dbio.1996.0332
DO - 10.1006/dbio.1996.0332
M3 - Article
C2 - 8954731
AN - SCOPUS:0030589702
SN - 0012-1606
VL - 180
SP - 605
EP - 617
JO - Developmental Biology
JF - Developmental Biology
IS - 2
ER -