The developing vertebrate central nervous system (CNS) generates its diverse repertoire of neurons and glia from few types of neural progenitors. Radial glia are a prominent type of neuroglial progenitor cells in the CNS and their differentiation is likely to be regulated by a secreted protein Meteorin. While investigating the role of meteorin(metrn) gene in zebrafish, we determined that both metrn and its paralog metrnl1 are expressed within the developing neural tube in temporally overlapping but spatially discrete patterns. Our gain of expression studies based on mRNA injections of both metrn and metrnl, individually and in combination suggest that these genes act synergistically and yield phenotypes such as cyclopia and mid-hindbrain boundary mispatterning resembling defects associated with genes of signaling morphogens such as shh and nodal. In contrast, morpholino induced knockdown of metrn alone induced severe reduction in brain size but not cyclopia. Thus, we hypothesize that: 1) metrn and metrnl may either directly function as morphogens or indirectly converge onto other morphogen signaling pathways, and 2) expression levels of both metrn and metrnl genes must be tightly regulated during normal CNS development. A CRISPR insertion mutant previously generated in our lab failed to show phenotype despite expressing the aberrant RNA as its predicted translation indicates an alternate initiation downstream of the mutation could produce a polypeptide that only lacks the signal sequence. We are thus creating promoterless knockouts to altogether abrogate expression of both metrn and metrnl and describe the characterization of promoter elements targeted in this analysis. A poster derived from Special Studies and STRIDE program with Dr. Michael Barresi, Professor of Biological Sciences and Dr. Narendra Pathak, Laboratory Instructor in Neuroscience.
by Georgia Krikorian '22 and Dahlia Rodriguez '21 AC