Proliferation and patterning are mediated independently in the dorsal spinal cord downstream of canonical Wnt signaling.
Canonical Wnt signaling can regulate proliferation and patterning in the developing spinal cord, but the relationship between these functions has remained elusive. It has been difficult to separate the distinct activities of Wnts because localized changes in proliferation could conceivably alter patterning, and gain and loss of function experiments have resulted in both types of defects. To resolve this issue we have investigated canonical Wnt signaling in the zebrafish spinal cord using multiple approaches. We demonstrate that Wnt signaling is required initially for proliferation throughout the entire spinal cord, and later for patterning dorsal progenitor domains. Furthermore, we find that spinal cord patterning is normal in embryos after cell division has been pharmacologically blocked. Finally, we determine the transcriptional mediators of Wnt signaling that are responsible for patterning and proliferation. We show that tcf7 gene knockdown results in dorsal patterning defects without decreasing the mitotic index in dorsal domains. In contrast, tcf3 gene knockdown results in a reduced mitotic index without affecting dorsal patterning. Together, our work demonstrates that proliferation and patterning in the developing spinal cord are separable events that are regulated independently by Wnt signaling.
Department of Neurobiology and Anatomy University, Utah School of Medicine, Salt Lake City, UT 84132, USA.
Jennifer
J
Bonner
Suzanna L
SL
Gribble
Eric S
ES
Veien
O Brant
OB
Nikolaus
Gilbert
G
Weidinger
Richard I
RI
Dorsky
D000818:Animals; D019521:Body Patterning; D004625:Embryo, Nonmammalian; D018507:Gene Expression Regulation, Developmental; D015398:Signal Transduction; D013116:Spinal Cord / Q000196:embryology* / Q000378:metabolism*; D051820:TCF Transcription Factors / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism; D058125:Transcription Factor 7-Like 1 Protein; D051153:Wnt Proteins / Q000378:metabolism*; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
D051820:TCF Transcription Factors; C503185:Tcf7 protein, zebrafish; D015534:Trans-Activators; D058125:Transcription Factor 7-Like 1 Protein; D051153:Wnt Proteins; D029961:Zebrafish Proteins