ABSTRACT
The semaphorin/collapsin gene family is a large and diverse family encoding both secreted and transmembrane proteins, some of which are thought to act as repulsive axon guidance molecules. However, the function of most semaphorins is still unknown. We have cloned and characterized several semaphorins in the zebrafish in order to assess their in vivo function. Zebrafish semaZ2 is expressed in a dynamic and restricted pattern during the period of axon outgrowth that indicates potential roles in the guidance of several axon pathways. Analysis of mutant zebrafish with reduced semaZ2 expression reveals axon pathfinding errors that implicate SemaZ2 in normal guidance.
Subject(s)
Nerve Growth Factors/physiology , Nerve Tissue Proteins/physiology , Zebrafish Proteins , Amino Acid Sequence , Animals , Axons/physiology , Branchial Region/embryology , Central Nervous System/embryology , Chickens , Gene Expression Regulation, Developmental , Mesencephalon/embryology , Molecular Sequence Data , Mutation , Nerve Growth Factors/genetics , Nerve Tissue Proteins/genetics , Neural Crest/embryology , Notochord/embryology , Prosencephalon/embryology , RNA, Messenger , Rhombencephalon/embryology , Semaphorins , Sequence Homology, Amino Acid , Spinal Cord/embryology , Zebrafish/embryology , Zebrafish/genetics , Zebrafish/physiologyABSTRACT
The large, conserved semaphorin/collapsin gene family encodes putative axon guidance molecules. We describe the cloning and expression of two n ovel zebrafish semaphorins that represent an increase in the size and diversity of the family. These semaphorins are expressed in unique and dynamic patterns during development.
Subject(s)
Gene Expression Regulation, Developmental , Nerve Growth Factors/genetics , Proteins/genetics , Zebrafish/embryology , Zebrafish/genetics , Amino Acid Sequence , Animals , Brain/embryology , Brain/metabolism , Branchial Region/embryology , Branchial Region/metabolism , Cloning, Molecular , Embryo, Nonmammalian , In Situ Hybridization , Molecular Sequence Data , Nervous System/embryology , Nervous System/metabolism , Proteins/metabolism , Semaphorins , Sequence Homology, Amino AcidABSTRACT
We have identified Math5, a mouse basic helix-loop-helix (bHLH) gene that is closely related to Drosophila atonal and Xenopus Xath5 and is largely restricted to the developing eye. Math5 retinal expression precedes differentiation of the first neurons and persists within progenitor cells until after birth. To position Math5 in a hierarchy of retinal development, we compared Math5 and Hes1 expression in wild-type and Pax6-deficient (Sey) embryos. Math5 expression is downregulated in Sey/+ eyes and abolished in Sey/Sey eye rudiments, whereas the bHLH gene Hes1 is upregulated in a similar dose-dependent manner. These results link Pax6 to the process of retinal neurogenesis and provide the first molecular correlate for the dosage-sensitivity of the Pax6 phenotype. During retinogenesis, Math5 is expressed significantly before NeuroD, Ngn2 or Mash1. To test whether these bHLH genes influence the fates of distinct classes of retinal neurons, we ectopically expressed Math5 and Mash1 in Xenopus retinal progenitors. Unexpectedly, lipofection of either mouse gene into the frog retina caused an increase in differentiated bipolar cells. Directed expression of Math5, but not Xath5, in Xenopus blastomeres produced an expanded retinal phenotype. We propose that Math5 acts as a proneural gene, but has properties different from its most closely related vertebrate family member, Xath5.
