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Floor Plate

Floor Plate. Issues Diversity Non-neuronal cells Neurons Developmental origins Midbrain dopaminergic cells Comparison to insect midline cells. Spinal Cord Development. Notochord Induction of Floor Plate Formation in Mammals and Chicks. Shh.

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Floor Plate

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  1. Floor Plate Issues • Diversity • Non-neuronal cells • Neurons • Developmental origins • Midbrain dopaminergic cells • Comparison to insect midline cells

  2. Spinal Cord Development

  3. Notochord Induction of Floor Plate Formation in Mammals and Chicks Shh

  4. Floor Plate: Shh Induction of Spinal Cord Development • Shh Induction of Spinal Cord Development • Patterns ventral spinal cord • v3, MN, v2, v1, v0

  5. Floor Plate: Control of Axon Crossing • Control of axon crossing • Netrins • Shh

  6. Zebrafish Floor Plate Description • Early description (Kuwada 1990) • Consists of 3 rows of cells • Defined by cuboidal shape, and most extend no processes (non-neuronal) • Among earliest identifiable cells in spinal cord and appear before first growth cones • Crossing growth cones are between FP and basal lamina next to notochord

  7. Zebrafish Floor Plate Description • Two cell populations (Odenthal 2000) • Medial FP (MLP): shh+, netrin1+, fkd4+, fkd7+ • Lateral FP (LFP): foxa2 (fkh)+, fkd4+, netrin-1+

  8. Zebrafish MFP Genetics • MFP • cyclops (cyc; nodal-TGF-b), one-eyed pinhead (oep; EGF-CFC), schmalspur (sur; foxh1) result in absence of MFP but not LFP • LFP does not require MFP for development

  9. Zebrafish LFP Genetics • LFP • no-tail (ntl; fly brachyenteron), floating head (flh), momo (mom) have an absence of notochord • flh or mom: MFP present with associated LFP; LFP absent when MFP absent • In ntl: get expansion of MFP and LFP • LFP can develop without notochord (as can MFP), but LFP only in presence of MFP

  10. Shh Control of LFP • syu (sonic you: shh) • Affects LFP but not MFP • Inject syu RNA  increase LFP but not MFP

  11. Zebrafish Summary • Early cells decide to be either notochord or FP • MFP: notochord and shh-independent; requires nodal-related pathway (TGF-b) • LFP: dependent on shh from either Notochord or MFP • Species differences: • Murine and chicken shh from notochord is required for induction of all FP cells • Murine Shh and netrin-1 are only in MFP and foxa2 (fly fkh) broadly expressed • Chicken Foxa2 in MFP and shh and netrin-1 in LFP

  12. Multiple Floor Plate Cell types • Zebrafish (Schäfer 2007) • foxa2: all MFP; subset LFP • tal2 bHLH gene (fly ~HLH4C) in subset of foxa2– LFP • Insect comparison • Both insect midline and vertebrate FP consist of neurons and non-neuronal (glial) cell types

  13. Tal2+ LFP cells are Postmitotic • Label with pHH3 • Tal2+ cells negative • Foxa2 + tal2– cells positive • Tal2 + cells are postmitotic

  14. Multiple Floor Plate Cell types • Late stage embryonic FP • Sim1+ cells are LFP subset and postmitotic • Sim1+ cells express neuronal marker • Sim1+ cells are V3 interneurons (glutamatergic in other contexts) • Also observed GABAergic neurons

  15. Summary • Tal2 + cells are neuronal progenitor cells • Subset  sim1 + V3 interneurons • May also give rise to other interneurons • Tal2 – foxa2+ cells are non-neuronal • Insect comparison • Both insect ML and vertebrate have Sim + interneurons

  16. Notch Signaling • Mindbomb (Neur) mutant • Nkx2.2b (vnd), foxa2 (LFP non-neuronal cells), tal2 (LFP neurons) reduced or absent • Foxa2 in MFP (non-neuronal) normal • Notch signaling required for LFP and p3 neurons wt mib wt mib

  17. Shh Signaling • In shh mutants, p3 LFP cells absent • In dtr/+ and yot/+ foxa2 LFP was absent and tal2 and sim1 normal • Thus, non-neuronal LFP cells require high Shh levels compared to p3 cells

  18. Summary • Early • foxa2 + cells proliferate • Tal2 + cells are postmitotic and differentiate into neurons • Later • Subset of tal2+ cells become sim1 + V3 interneurons • Also GABAergic KA neurons (sim1 +?) • Notch signaling required for LFP and p3 cells • Shh signaling: LFP non-neuronal and neuronal cells required different levels of Shh

  19. Midbrain FP Cells • Midbrain dopaminergic neurons • Motor control, reward, addiction, attention, cognition • Loss results in Parkinson disease • Origins: mouse (Kittappa 2007) • TH+ cells are in foxa2+ FP cells in midbrain

  20. Midbrain FP Cells • Shh is expressed in FP • Shh-cre X R26R lacZ reporter: lineage marker • TH+ cells overlap with b-Gal

  21. Development of Midbrain FP Cells Dorsal fate 5-HT1a fate

  22. Midbrain FP Cells • Progenitor cell development • Shh: induces FP • Otx2: required for generation of mesDA precursors • Lmx1a (CG32105): required for mesDA cell fate • Ngn2: proneural function • Postmitotic development • Nurr1: controls subset of mesDA gene expression (TH) • Lmx1b (CG4328): survival; affects Pitx3 but not other genes (Nurr1, early TH) • Pitx3: lose TH expression, affects migration, survival • En: required for late maturation and survival

  23. Foxa2 • Kittappa 2007 • Foxa2–/– • No TH+ cells • Foxa2+/– • Motor defects • Loss of DA neurons • Like PD

  24. En • En (Simon 2004) • En is gradually expressed in TH + cells • En –/– • Early TH+ cells present but lack fibers • Late TH+ cells absent

  25. Summary • Vertebrate FP:insect ML • Diversity of neuronal and non-neuronal cell types • MG = non-neuronal FP; both important signaling centers • Sim+ cells present • DA+ cells present • Genes?

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