Lipids, membranes, and neurogenesis: A developmental continuum

Abstract

Lipids, including fats, waxes and sterols, are a group of naturally occurring cellular molecules that perform a diverse array of vital functions within every organism. Broadly, lipids directly or indirectly participate in signaling, act as building blocks within membranes, and function as highly efficient sources of energy. In all these roles, lipids can heavily influence the chemical activities that sustain life-processes collectively known as metabolism. Lipids are composed of fatty acids and particularly, the lipids that constitute biological membranes are composed of long chain fatty acids. Long chain fatty acids, in order to be used for energy generation, membrane biogenesis, or signaling within the cell, need to be activated by esterification to Coenzyme-A. Long chain Acyl CoA Synthase enzymes catalyze this important esterification reaction and hence act as key metabolic regulators of fatty acid metabolism within the cell. The membrane fatty acid composition of a cell determines the protein composition of biological membranes and can thus define the developmental fate of a cell as well as its membrane bending and migratory abilities. In this regard, Acyl CoA Synthases can also act as key developmental regulators. In the current study, we present evidence for the role of Long chain Acyl CoA Synthases (ACSL): Bgm and Dbb in Drosophila embryogenesis. Particularly, maternally deposited bgm transcript is required for the processes of iv cellularization and neurogenesis during Drosophila embryonic development. Rab-5 tagged endocytic vesicles are critical sources of membrane components during cellularization, and Bgm is required for the proper subcellular targeting of these vesicles. Neurogenesis also requires maternal expression of bgm, and abnormal neurogenesis in bgm mutants appears to be related to the early defect in cellularization. In addition, we also demonstrate that bgm and dbb are duplicated genes with partially diverged developmental expression patterns and are transcriptionally regulated by dorsoventral patterning genes. Lastly, we provide evidence for behavioral abnormalities in bgm and dbb mutant flies, thus making them attractive models of neurodegenerative disorders, which can be potentially used in large scale screens for diet and drug therapies.