The AP-2 Transcription Factor APTF-2 Is Required for Neuroblast and Epidermal Morphogenesis in Caenorhabditis elegans Embryogenesis

Abstract

The evolutionarily conserved family of AP-2 transcription factors (TF) regulates proliferation, differentiation, and apoptosis. Mutations in human AP-2 TF have been linked with bronchio-occular-facial syndrome and Char Syndrome, congenital birth defects characterized by craniofacial deformities and patent ductus arteriosus, respectively. How mutations in AP-2 TF cause the disease phenotypes is not well understood. Here, we characterize the aptf-2(qm27) allele in Caenorhabditis elegans, which carries a point mutation in the conserved DNA binding region of AP-2 TF. We show that compromised APTF-2 activity leads to defects in dorsal intercalation, aberrant ventral enclosure and elongation defects, ultimately culminating in the formation of morphologically deformed larvae or complete arrest during epidermal morphogenesis. Using cell lineaging, we demonstrate that APTF-2 regulates the timing of cell division, primarily in ABarp, D and C cell lineages to control the number of neuroblasts, muscle and epidermal cells. Live imaging revealed nuclear enrichment of APTF-2 in lineages affected by the qm27 mutation preceding the relevant morphogenetic events. Finally, we found that another AP-2 TF, APTF-4, is also essential for epidermal morphogenesis, in a similar yet independent manner. Thus, our study provides novel insight on the cellular-level functions of an AP-2 transcription factor in development.

SOX11 promotes invasive growth and ductal carcinoma in situ progression

“…ALDH1A1 plays a role in the proliferation and differentiation of mammary progenitor cells in the normal breast; clonogenicity is decreased upon ALDH1A1 knockdown . TFAP2B is thought to stimulate cell proliferation and suppress terminal differentiation of specific cell types during embryonic development . Mutations in TFAP2B cause Char syndrome, a disorder characterized by defective heart, craniofacial and limb development .…”

Notch-Directed Germ Cell Proliferation Is Mediated by Proteoglycan-Dependent Transcription

“…We found that aptf-2 RNAi reduced GLP-1::V5 expression in the distal end of the germline (Figure 4B-C). In addition, aptf-2 RNAi lowered PZ germ cell number, as did an aptf-2(qm27) mutant that harbors a point mutation in the APTF-2 DNA binding domain (Figure 4Dand S6)(Budirahardja et al, 2016). In contrast, RNAi knockdown of aptf-1 and aptf-3/4 caused non-significant changes to GLP-1::V5 expression and PZ germ cell number (Figure 4B-D and S6).…”

“…Syndecans are a family of transmembrane proteoglycans that play important roles in metazoan development, regeneration, tissue repair and homeostasis (Afratis et al, 2017). Syndecans consist of conserved cytoplasmic and transmembrane domains and more divergent ectodomains that carry differentially sulfated glycosaminoglycan (GAG) chains (Choi et al, 2011). These GAG chains consist of heparan sulfate (HS) and chondroitin sulfate (CS) that can interact with ligands, extracellular matrix proteins, cytokines, growth factors and small molecules to coordinate signaling, cell adhesion and host defence mechanisms (Choi et al, 2011).…”

“…Syndecans consist of conserved cytoplasmic and transmembrane domains and more divergent ectodomains that carry differentially sulfated glycosaminoglycan (GAG) chains (Choi et al, 2011). These GAG chains consist of heparan sulfate (HS) and chondroitin sulfate (CS) that can interact with ligands, extracellular matrix proteins, cytokines, growth factors and small molecules to coordinate signaling, cell adhesion and host defence mechanisms (Choi et al, 2011). Previously, we showed that syndecans control intrinsic cell behavior by regulating transient receptor potential canonical (TRPC) Ca 2+ channels to maintain optimal Ca 2+ influx over the plasma membrane (Gopal et al, 2015).…”

Novel TFAP2A mutation in a Japanese family with Branchio-oculo-facial syndrome

“…One-third of patients with BOFS also exhibit renal system anomalies 1 . Transcription factor AP2-alpha ( TFAP2A , OMIM number: 107580) is known to be the gene responsible for the development of BOFS, and specific TFAP2A functions have been elucidated in the affected tissues of patients with BOFS 2 – 5 . In the current report, we describe a family that has multiple anomalies that are clinically consistent with the BOFS spectrum and present results from genetic analysis of the affected members.…”