Academic journal article Genetics

Transmembrane Proteins UNC-40/DCC, PTP-3/LAR, and MIG-21 Control Anterior-Posterior Neuroblast Migration with Left-Right Functional Asymmetry in Caenorhabditis Elegans

Academic journal article Genetics

Transmembrane Proteins UNC-40/DCC, PTP-3/LAR, and MIG-21 Control Anterior-Posterior Neuroblast Migration with Left-Right Functional Asymmetry in Caenorhabditis Elegans

Article excerpt

ABSTRACT Migration of neurons and neural crest cells is of central importance to the development of nervous systems. In Caenorhabditis elegans, the QL neuroblast on the left migrates posteriorly, and QR on the right migrates anteriorly, despite similar lineages and birth positions with regard to the left-right axis. Initial migration is independent of a Wnt signal that controls later anterior-posterior Q descendant migration. Previous studies showed that the transmembrane proteins UNC-40/DCC and MIG-21, a novel thrombospondin type I repeat containing protein, act redundantly in left-side QL posterior migration. Here we show that the LAR receptor protein tyrosine phosphatase PTP-3 acts with MIG-21 in parallel to UNC-40 in QL posterior migration. We also show that in right-side QR, the UNC-40 and PTP-3/MIG-21 pathways mutually inhibit each other's role in posterior migration, allowing anterior QR migration. Finally, we present evidence that these proteins act autonomously in the Q neuroblasts. These studies indicate an inherent left-right asymmetry in the Q neuroblasts with regard to UNC-40, PTP-3, and MIG-21 function that results in posterior vs. anterior migration.

CELL migration is a fundamental event in the development of nervous systems. In the vertebrate central nervous system, neurons and neuroblasts migrate radially to populate distinct layers in the cerebellar and cerebral cortices, and neural crest cells migrate along distinct paths in the vertebrate embryo to give rise to the peripheral nervous system. The Q neuroblasts in Caenorhabditis elegans are a useful model to study the migration of neuroblasts and neurons in the anterior-posterior axis. The Q neuroblasts are a bilaterally symmetric pair of cells in the posterior-lateral region of the animal, with QR on the right side and QL on the leftside (Sulston and Horvitz 1977). The Q neuroblasts are born in embryogenesis and are the sisters of the V5 hypodermal seam cells. By 5 hr after hatching, QR has migrated anteriorly and divided over the V4 seam cell, and QL has migrated posteriorly and divided over the V5 seam cell (Honigberg and Kenyon 2000; Chapman et al. 2008; Dyer et al. 2010). The resulting Q cell descendants then undergo a pattern of migration, division, and programmed cell death resulting in three neurons each (AQR, SDQR, and AVM on the right from QR; and PQR, SDQL, and PVM on the leftfrom QL) (Sulston and Horvitz 1977; Chalfie and Sulston 1981). The QR descendant AQR migrates the longest distance to a region near the anterior deirid ganglion in the head, and the QL descendant PQR migrates the longest distance posteriorly to the phasmid ganglion in the tail (Sulston and Horvitz 1977; White et al. 1986; Chapman et al. 2008). The posterior migration of QL descendants requires the activity of the MAB-5/Hox transcription factor, expression of which is induced in QL descendants by an EGL-20/Wnt signal emanating from the posterior (Chalfie et al. 1983; Kenyon 1986; Salser and Kenyon 1992; Harris et al. 1996;Whangbo and Kenyon 1999; Korswagen et al. 2000; Herman 2003; Eisenmann 2005). QR migrates anteriorly and does not normally receive this EGL-20/Wnt signal, and thus does not express MAB-5/Hox.

The initial anterior and posterior migrations of the QR and QL neuroblasts do not depend on MAB-5 or EGL-20/Wnt (Chapman et al. 2008), as QL and QR protrude and polarize normally in mab-5 and egl-20 mutants. While initial Q migration is independent of EGL-20/Wnt, the five Wnt genes are involved in subsequent Q descendant guidance along the anterior-posterior axis (Pan et al. 2006; Harterink et al. 2011; Zinovyeva et al. 2008).

The initial Q migrations can affect subsequent MAB-5 expression in the Q descendants (Chapman et al. 2008; Middelkoop et al. 2012). The extent of posterior protrusion correlates with mab-5 expression, with more mab-5 expression in cells that protrude posteriorly (Middelkoop et al. 2012), consistent with exposure to the posterior EGL-20/Wnt signal. …

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