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Related Research Units

Genetics and Genomics Research
F.M. Kirby Neurobiology Center

Research Overview

The goal of the Heiman lab is to understand how cells get their shapes and assemble into organs. Defects in this process lead to structural birth defects. We are using forward genetic approaches in C. elegans to identify the genes that give individual cells their characteristic shapes and that specify defined cell-cell contacts.

Laboratory Projects

  1. Dendrite length: Using forward genetic screens, we have identified two distinct mechanisms by which sensory dendrites attain the right lengths. Surprisingly, both mechanisms involve an “anchorand- stretch” process in which dendritic endings anchor to defined sites on neighboring glial partners and then undergo mechanical pulling to reach their final lengths.

  2. Selective attraction and repulsion: A major organizing force in the nervous system is selective attraction and repulsion between neurons. We are identifying cell-surface adhesion molecules that mediate selective bundling (fasciculation) of dendrites. We have also shown how contact-mediated repulsion between dendrites can give rise to complex emergent patterning.

  3. Glial diversity: Glial cells adopt a diverse array of morphologies, presumably corresponding to diverse molecular and cellular functions. Although mechanisms that give rise to neuronal diversity are well characterized, we know relatively little about how different glial cell fates are specified. We are identifying transcriptional regulators that activate or repress the fate of specific glial subtypes.

Research Background

Dr. Heiman received his Ph.D. from UCSF (1997-2003), where he workedwith Dr. Peter Walter and identified the first genes shown to be required forcell-cell fusion during yeast mating. He received his postdoctoral training at Rockefeller University (2003-2011) with Dr. Shai Shaham, where he studied the genetic control of cell shape using the sensory neurons and glia of C.elegans as a model system. In 2011, he started his own research group jointly between the Division of Genetics at Boston Children’s Hospital and the Department of Genetics at Harvard Medical School. He has been an HHMI predoctoral fellow, a Jane Coffin Childs postdoctoral fellow, and a March of Dimes Basil O’Connor Scholar, and he is the recipient of an unnamed chair in Genetics at Boston Children’s Hospital. He is currently an Assistant Professor of Genetics and Pediatrics.

Selected Publications

  1. Yip Z. C. and Heiman M. G. (2016) Duplication of a single neuron in C. elegans reveals a pathway for dendrite tiling by mutual repulsion. Cell Reports. 15:2109-2117.
  2. Gilleland C. L., Falls A. T., Noraky J., Heiman M. G.*, Yanik M.F.* (2015) Computer-assisted transgenesis of Caenorhabditis elegans for deep phenotyping. Genetics. 201: 39-46. *, co-corresponding.
  3. Heiman M. G. and Shaham S. (2009) DEX-1 and DYF-7 establish sensory dendrite length by anchoring dendritic tips during cell migration. Cell. 137: 344-355.

Publications

  1. Specialized structure and function of the apical extracellular matrix at sense organs. Cells Dev. 2024 Sep; 179:203942. View Abstract
  2. Dendrite morphogenesis in Caenorhabditis elegans. Genetics. 2024 06 05; 227(2). View Abstract
  3. SAX-7/L1CAM acts with the adherens junction proteins MAGI-1, HMR-1/Cadherin, and AFD-1/Afadin to promote glial-mediated dendrite extension. bioRxiv. 2024 Jan 11. View Abstract
  4. A sex-specific switch in a single glial cell patterns the apical extracellular matrix. Curr Biol. 2023 10 09; 33(19):4174-4186.e7. View Abstract
  5. A sex-specific switch in a single glial cell patterns the apical extracellular matrix. bioRxiv. 2023 Mar 18. View Abstract
  6. When is a neuron like an epithelial cell. Dev Biol. 2022 09; 489:161-164. View Abstract
  7. Axon-dendrite and apical-basolateral sorting in a single neuron. Genetics. 2022 05 05; 221(1). View Abstract
  8. Loss of the Extracellular Matrix Protein DIG-1 Causes Glial Fragmentation, Dendrite Breakage, and Dendrite Extension Defects. J Dev Biol. 2021 Oct 07; 9(4). View Abstract
  9. Lineage-specific control of convergent differentiation by a Forkhead repressor. Development. 2021 10 01; 148(19). View Abstract
  10. Cell-type-specific promoters for C. elegans glia. J Neurogenet. 2020 Sep-Dec; 34(3-4):335-346. View Abstract
  11. Dendrites with specialized glial attachments develop by retrograde extension using SAX-7 and GRDN-1. Development. 2020 02 17; 147(4). View Abstract
  12. Long-term activity drives dendritic branch elaboration of a C. elegans sensory neuron. Dev Biol. 2020 05 01; 461(1):66-74. View Abstract
  13. Morphogenesis of neurons and glia within an epithelium. Development. 2019 02 20; 146(4). View Abstract
  14. A multicellular rosette-mediated collective dendrite extension. Elife. 2019 02 15; 8. View Abstract
  15. Ordered arrangement of dendrites within a C. elegans sensory nerve bundle. Elife. 2018 08 20; 7. View Abstract
  16. A neuronal MAP kinase constrains growth of a Caenorhabditis elegans sensory dendrite throughout the life of the organism. PLoS Genet. 2018 06; 14(6):e1007435. View Abstract
  17. Coordinated morphogenesis of neurons and glia. Curr Opin Neurobiol. 2017 12; 47:58-64. View Abstract
  18. A Conserved Role for Girdin in Basal Body Positioning and Ciliogenesis. Dev Cell. 2016 09 12; 38(5):493-506. View Abstract
  19. Duplication of a Single Neuron in C. elegans Reveals a Pathway for Dendrite Tiling by Mutual Repulsion. Cell Rep. 2016 06 07; 15(10):2109-2117. View Abstract
  20. Computer-Assisted Transgenesis of Caenorhabditis elegans for Deep Phenotyping. Genetics. 2015 Sep; 201(1):39-46. View Abstract
  21. FBN-1, a fibrillin-related protein, is required for resistance of the epidermis to mechanical deformation during C. elegans embryogenesis. Elife. 2015 Mar 23; 4. View Abstract
  22. The many glia of a tiny nematode: studying glial diversity using Caenorhabditis elegans. Wiley Interdiscip Rev Dev Biol. 2015 Mar-Apr; 4(2):151-60. View Abstract
  23. Shaping dendrites with machinery borrowed from epithelia. Curr Opin Neurobiol. 2013 Dec; 23(6):1005-10. View Abstract
  24. Neurons at the extremes of cell biology. Mol Biol Cell. 2011 Mar 15; 22(6):721. View Abstract
  25. Structure of sterol aliphatic chains affects yeast cell shape and cell fusion during mating. Proc Natl Acad Sci U S A. 2010 Mar 02; 107(9):4170-5. View Abstract
  26. Twigs into branches: how a filopodium becomes a dendrite. Curr Opin Neurobiol. 2010 Feb; 20(1):86-91. View Abstract
  27. DEX-1 and DYF-7 establish sensory dendrite length by anchoring dendritic tips during cell migration. Cell. 2009 Apr 17; 137(2):344-55. View Abstract
  28. Ancestral roles of glia suggested by the nervous system of Caenorhabditis elegans. Neuron Glia Biol. 2007 Feb; 3(1):55-61. View Abstract
  29. The Golgi-resident protease Kex2 acts in conjunction with Prm1 to facilitate cell fusion during yeast mating. J Cell Biol. 2007 Jan 15; 176(2):209-22. View Abstract
  30. Prm1p, a pheromone-regulated multispanning membrane protein, facilitates plasma membrane fusion during yeast mating. J Cell Biol. 2000 Oct 30; 151(3):719-30. View Abstract

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