Lecture 10 Types of lineage mutants Lateral inhibition in C. elegans Induction in C. elegans

Mutant names and origins Most isolated in general mutant screens unc Uncoordinated dpy Dumpy short and fat lin lineage abnormal egl egg laying let lethal

Mutant names and origins Phenotypic class ie screen isolated in Complementation group unc-93 (e1400) allele lin-22(n372)

Cell lineage mutants Canonical cell lineage Stem cell like mutant lineages Homeotic mutant lineages Heterochronic mutant lineages

Canonical cell lineage Horvitz The Nematode C. elegans 1988

Canonical cell lineage A BC Horvitz The Nematode C. elegans 1988

Canonical cell mutant lineages A BC A BA A BB wild-type

Canonical cell mutant lineages A BC A BA A BB wild-type Regeneration of the mother cell fate: stem cell like

Stem cell like mutant lineages Horvitz The Nematode C. elegans 1988

Canonical cell mutant lineages A BC A BA A BB wild-type Sisters have the same fate: homeotic

Homeotic transformation The transformation of one body part into the likeness of another

Antennapedia can be misexpressed either by spontaneous mutation or by genetic engineering. Antenna to second leg transformation hsp Antpry +

Canonical cell mutant lineages A BC A BA A BB wild-type Sisters have the same fate: homeotic

Cell lineage homeotic transformation Horvitz The Nematode C. elegans 1988

Homeotic transformation of several lineages Horvitz The Nematode C. elegans 1988

Heterochronic genes Slack and Ruvkun Annu. Rev. Genet. 31, 611

Heterochronic genes Slack and Ruvkun Annu. Rev. Genet. 31, 611

Heterochronic genes Precious development of L2 lineage Slack and Ruvkun Annu. Rev. Genet. 31, 611

Heterochronic genes Suppression of L2 lineage and replacement with L1 lineage. Slack and Ruvkun Annu. Rev. Genet. 31, 611

Heterochronic genes lin-14 activity L1 L2 wtlin14 l f lin14 gf ON OFF

Heterochronic genes Slack and Ruvkun Annu. Rev. Genet. 31, 611

Heterochronic genes Slack and Ruvkun Annu. Rev. Genet. 31, 611

Heterochronic genes lin-4 lin-14

Heterochronic genes lin-14 encodes a nuclear protein lin-4 encodes a non-coding RNA a micro-RNA-the first found

Heterochronic genes lin-4 RNA base pairs with the lin-14 3’ UTR In lin-14 gf mutants the lin-4 binding sites are deleted. Slack and Ruvkun Annu. Rev. Genet. 31, 611

Heterochronic genes Levels L1L2L3L4 lin-14 mRNA

Heterochronic genes Levels L1L2L3L4 lin-14 protein

Heterochronic genes Levels L1L2L3L4 lin-14 protein lin-4 micRNA

Temporal Morphogen hypothesis Kalthoff Analysis of Biological development 2nd ed

Lateral inhibition Order arising from nothing: an emergent property Gilbert Developmental Biology 5th ed

Lateral inhibition Order arising from nothing: an emergent property Gilbert Developmental Biology 5th ed

Z1.ppp Z4.aaa Individual AIndividual B Anchor cell/ Ventral uterine cell equivalence group AC VU

Model for AC/VU decision Gilbert Developmental Biology 5th ed

Model for AC/VU decision Equivalent signaling Gilbert Developmental Biology 5th ed

Model for AC/VU decision Stochastic difference in signaling Gilbert Developmental Biology 5th ed

Model for AC/VU decision Differential expression of receptor and ligand Gilbert Developmental Biology 5th ed

Model for AC/VU decision Determined cell fates Gilbert Developmental Biology 5th ed

Genetic analysis of lateral inhibition lin-12 gf lin-12 +(wt) lin-12 lf Z1.pppZ4.aaa VU AC/VU AC

Mosaic analysis in C. elegans ncl-1 lin-12 ncl-1 + lin-12 + qDp3 qDp3 is a free duplication that is mitotically unstable and is lost forming clones of ncl-1 lin-12 cells

Mosaic analysis in C. elegans ncl-1 + ncl-1 In ncl-1 cells, the nucleolus is large.

Mosaic analysis in C. elegans ncl-1 lin-12 cell Seydoux and Greenwald Cell 57, 1237

Z1.ppp Z4.aaa Individual AIndividual B AC VU lin-12 + lin-12 Mosaic analysis in C. elegans

Z1.ppp Z4.aaa Individual AIndividual B AC VU lin-12 + lin-12 Mosaic analysis in C. elegans Lin-12 activity is required in the VU cell

Model for AC/VU decision Gilbert Developmental Biology 5th ed

Precommitment Committed Expression of Lin-12 protein Levitan and Greenwald Development 125, 3101

Induction of the vulva in C. elegans

Vulva equivalence group Wormbase

Induction of the vulva in C. elegans Horvitz and Sternberg Nature 351, 535

Induction of the vulva in C. elegans Horvitz and Sternberg Nature 351, 535

Induction of the vulva in C. elegans Horvitz and Sternberg Nature 351, 535

Induction of the vulva in C. elegans Horvitz and Sternberg Nature 351, 535

Induction of the vulva in C. elegans Horvitz and Sternberg Nature 351, 535

Induction of the vulva in C. elegans Horvitz and Sternberg Nature 351, 535

Induction of the vulva in C. elegans wild-type Vulvaless Vul Multivulva Muv Ferguson and Horvitz Genetics 110, 17

Induction of the vulva in C. elegans Ferguson et al. Nature 326, 259

Induction of the vulva in C. elegans Wormbase

At high concentration of Lin-3: 1° fate At medium concentration of Lin-3: 2° fate At low concentration of Lin-3: 3° fate Lin-3 a morphogen?