Functional Diversification of the Four MARCKS Family Members in Zebrafish Neural Development

Abstract

Myristoylated alanin-rich C-kinase substrate (MARCKS) and MARCKS-like 1, each encoded by a different gene, comprise a very small family of actin-modulating proteins with essential roles in mammalian neural development. We show here that four genes (two marcks and two marcksl1) are present in teleosts including zebrafish, while ancient actinopterigians, sarcopterigian fishes, and chondrichtyans only have two. No marcks genes were found in agnaths or invertebrates. All four zebrafish genes are expressed during development, and we show here how their early knockdown causes defects in neural development, with some phenotypical differences. Knockdown of marcksa generated embryos with smaller brain and eyes, while marcksb caused different morphogenetic defects, such as larger hindbrain ventricle and folded retina. marcksl1a and marcksl1b morpholinos also caused smaller eyes and brain, although marcksl1a alone generated larger brain ventricles. At 24 hpf, marcksb caused a wider angle of the hindbrain walls, while marcksl1a showed a "T-shaped" neural tube and alterations in neuroepithelium organization. The double knockdown surprisingly produced new features, which included an increased neuroepithelial disorganization and partial neural tube duplications evident at 48 hpf, suggesting defects in convergent extension. This disorganization was also evident in the retina, although retinal ganglion cells were still able to differentiate. marcksl1b morphants presented a unique retinal phenotype characterized by the occurrence of sporadic ectopic neuronal differentiation. Although only marcksl1a morphant had a clear "ciliary phenotype," all presented significantly shorter cilia. Altogether, our data show that all marcks genes have functions in zebrafish neural development, with some differences that suggest the onset of protein diversification.

Role of Protein Kinase C in Bipolar Disorder: A Review of the Current Literature

“…MARCKS is a membrane-bound actin crosslinking protein that regulates vesicular trafficking and mobility of structural phospholipids such as phosphatidylinositol-4,5-bisphosphate (PIP2) in the membrane plane [110,111]. MARCKS undergoes dissociation from the membrane and translocates to cytoplasm after phosphorylation by PKC [112].…”

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“…The 24 hpf zebrafish embryos, with and without chorion, were exposed to GAT1033 for 18 h. Image acquisition was made with a Leica TCS-SP5 laser scanning confocal microscope (Leica Microsystems GmbH, Wetzlar, Germany) using LASAF v. 2 software (Leica Microsystems, Wetzlar, Germany) and observed using a 405-nm laser excitation line and an emission bandwidth from 428–646 nm under a 20 × water immersion objective. Further image analysis, including quantitation, and processing of figures were made using Fiji ( ) [ 44 ].…”

Terminal Uridylyltransferases Execute Programmed Clearance of Maternal Transcriptome in Vertebrate Embryos

“…The calmodulin-binding proteins are regulated by calcium waves in the earliest cell cycles and play important roles in early development (Webb and Miller, 2000). For example, Marcks proteins, which are involved in gastrulation and neural development (Ott et al, 2011;Prieto and Zolessi, 2017), are encoded by transcripts with long poly(A) tails (69.9 and 37.9 nt for marcksb and marcksa, respectively). Some 3 0 UTR binding proteins also have long tails (40.2, 42.2, and 39.7 nt for cpeb1b, cth1, and cirbpa, respectively), which implies that they may be translated prior to the MZT and bootstrap the transcriptome to control their fates in later stages.…”