Shootin‐1 is required for nervous system development in zebrafish

Abstract

Background: Semaphorin6A (Sema6A) and its PlexinA2 (PlxnA2) receptor canonically function as repulsive axon guidance cues. To understand downstream signaling mechanisms, we performed a microarray screen and identified the "clutch molecule" shootin-1 (shtn-1) as a transcriptionally repressed target. Shtn-1 is a key proponent of cell migration and neuronal polarization and must be regulated during nervous system development. The mechanisms of Shtn-1 regulation and the phenotypic consequences of loss of repression are poorly understood. Results: We demonstrate shtn-1 overexpression results in impaired migration of the optic vesicles, lack of retinal pigmented epithelium, and pathfinding errors of retinotectal projections. We also observed patterning defects in the peripheral nervous system. Importantly, these phenotypes were rescued by overexpressing PlxnA2. Conclusions: We demonstrate a functional role for repression of shtn-1 by PlxnA2 in development of the eyes and peripheral nervous system in zebrafish. These results demonstrate that careful regulation of shtn-1 is critical for development of the nervous system.

Loss ofUBE3Aimpacts both neuronal and non-neuronal cells in human cerebral organoids

“…There was one cluster unknown with HSPs being the top gene markers (Unknown-HSP). Two small clusters were labeled as epithelial (e.g., KRT8 87 , TJP1 88 ) and endothelial cells (e.g., FLT1, 110,111 , SDK1 [90][91][92]112 , CAP2 113,114 , CTTNBP2 115,116 , FLRT2 [90][91][92]117,118 , DAB1 [119][120][121] , NBEA [90][91][92]122,123 ), axon/dendrite development (LIN7A 109 , EPHA5 110,111 , SDK1 [90][91][92]112 , CAP2 113,114 , CTTNBP2 115,116 , FLRT2 [90][91][92]117,118 , NELL2 124 , NFIB 125 , MYO5B 126 , ARPP21 127 , EPHA7 128,129 , NEO1 130 , SHTN1 [131][132][133] , SRGAP1 134 , SOX5 135 , DAB1 [119][120]…”

“…(E) Heatmap of top differentially expressed markers between EN-CL and non EN-CL neurons (EN, IN, Neuron, Neuron/IP, Neuron-HSP). Differentially expressed markers were grouped by cellular function: synapse-related ( SLC24A2 89–92 , LRRC7 93 , ANKS1B 94 , PLXND1 95 , SLC4A10 96 , LRRTM4 97 , KCNQ5 98 , GRIA3 90–92,99 , GRIA1 100 , DLGAP1 101 , CACNA1E 90–92,102 , ABHD6 103,104 , RIMS2 105–108 , LIN7A 109 , EPHA5 110,111 , SDK1 90–92,112 , CAP2 113,114 , CTTNBP2 115,116 , FLRT2 90–92,117,118 , DAB1 119–121 , NBEA 90–92,122,123 ), axon/dendrite development ( LIN7A 109 , EPHA5 110,111 , SDK1 90–92,112 , CAP2 113,114 , CTTNBP2 115,116 , FLRT2 90–92,117,118 , NELL2 124 , NFIB 125 , MYO5B 126 , ARPP21 127 , EPHA7 128,129 , NEO1 130 , SHTN1 131–133 , SRGAP1 134 , SOX5 135 , DAB1 119–121 ), cell migration/cortical layering ( LIN7A 109 , FLRT2 90–92,117,118 , NEO1 130 , SHTN1 131–133 , SRGAP1 134 , SOX5 135 , DAB1 119–121 , AFF3 136 , BCL11A 137 , ZBTB18 138,139…”