Zinc finger transcription factor Casz1 expression is regulated by homeodomain transcription factor Prrxl1 in embryonic spinal dorsal horn late‐born excitatory interneurons

Abstract

The transcription factor Casz1 is required for proper assembly of vertebrate vasculature and heart morphogenesis as well as for temporal control of Drosophila neuroblasts and mouse retina progenitors in the generation of different cell types. Although Casz1 function in the mammalian nervous system remains largely unexplored, Casz1 is expressed in several regions of this system. Here we provide a detailed spatiotemporal characterization of Casz1 expression along mouse dorsal root ganglion (DRG) and dorsal spinal cord development by immunochemistry. In the DRG, Casz1 is broadly expressed in sensory neurons since they are born until perinatal age. In the dorsal spinal cord, Casz1 displays a more dynamic pattern being first expressed in dorsal interneuron 1 (dI1) progenitors and their derived neurons and then in a large subset of embryonic dorsal late-born excitatory (dILB) neurons that narrows gradually to become restricted perinatally to the inner portion. Strikingly, expression analyses using Prrxl1-knockout mice revealed that Prrxl1, a key transcription factor in the differentiation of dILB neurons, is a positive regulator of Casz1 expression in the embryonic dorsal spinal cord but not in the DRG. By performing chromatin immunoprecipitation in the dorsal spinal cord, we identified two Prrxl1-bound regions within Casz1 introns, suggesting that Prrxl1 directly regulates Casz1 transcription. Our work reveals that Casz1 lies downstream of Prrxl1 in the differentiation pathway of a large subset of dILB neurons and provides a framework for further studies of Casz1 in assembly of the DRG-spinal circuit.

scRNA-Seq Reveals New Enteric Nervous System Roles for GDNF, NRTN, and TBX3

“…Furthermore, RBFOX1 regulates CNS neuron subtype differentiation, and CASZ1 and TBX2 regulate subtype specification in many cells including photoreceptors. 36 , 37 , 38 , 39 , 40 Normal colonic bead expulsion latency in Casz1 and Rbfox1 mutant mice suggests redundant ENS mechanisms prevent obvious anatomic or functional defects.…”

Spatiotemporal analysis of human intestinal development at single-cell resolution

“…For neuronal clusters; interneurons were identified by expression of tachkinin (TAC1) and enkephalin (PENK), inhibitory motor neuron by expression of nitric oxide (NOS1) and VIP and excitory motor neurons by expression of CASZ1 (Gulbransen and Sharkey, 2012;Monteiro et al, 2016), SLC5A7 and GFRA2 -the latter two genes were identified as part of the core transcriptional signature of excitory neurons in a recent scRNA-seq study of the ENS (Drokhlyansky et al, 2020). A cluster adjacent to the inhibitory motor cells expressed similar genes such as SCGN and NOS1, but at a lower level and was thus annotated as ''inhibitory motor neuron precursor.''…”

Effects of CASZI on bronchopulmonary development of neonatal rats

“…Vasculogenesis and angiogenesis are two major processes of vascular generation, the former is observed when the new blood vessels are formed by endothelial cells, endothelial progenitor cells or hemangioblastoma from nothing, and the latter is observed when the new blood vessels are formed based on the existing blood vessels through promoting the vascular endothelial cell migration and proliferation ( 9 , 10 ). Pulmonary angiogenesis involves a complex regulatory factors network, and several pro-vascular growth factors have been already discovered.…”