Lecture 10 Types of lineage mutants Lateral inhibition

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 lineage abnormal egg laying lethal

Mutant names and origins unc-93 (e 1400) Phenotypic class ie screen isolated in Complementation group lin-22(n 372) allele

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 B C Horvitz The Nematode C. elegans 1988

Canonical cell mutant lineages A B wild-type C A B B A

Canonical cell mutant lineages A B wild-type C Regeneration of the mother cell fate: stem cell like B B A A

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

Canonical cell mutant lineages A B B wild-type C Sisters have the same fate: homeotic A B A

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. + Antp ry hsp Antenna to second leg transformation

Canonical cell mutant lineages A B B wild-type C Sisters have the same fate: homeotic A B A

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 Precious development of L 2 lineage Slack and Ruvkun Annu. Rev. Genet. 31, 611

Heterochronic genes Suppression of L 2 lineage and replacement with L 1 lineage. Slack and Ruvkun Annu. Rev. Genet. 31, 611

Heterochronic genes L 1 wt lin 14 lf lin 14 gf ON OFF OFF ON lin-14 activity L 2

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 lin-14 m. RNA L 1 L 2 L 3 L 4

Levels Heterochronic genes lin-14 protein L 1 L 2 L 3 L 4

Levels Heterochronic genes lin-14 protein lin-4 mic. RNA L 1 L 2 L 3 L 4

Temporal Morphogen hypothesis Kalthoff Analysis of Biological development 2 nd ed

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

Anchor cell/ Ventral uterine cell equivalence group Individual A Z 1. ppp AC Z 4. aaa VU Individual B Z 1. ppp Z 4. aaa VU AC

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

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

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

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

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

Genetic analysis of lateral inhibition lin-12 gf +(wt) lf Z 1. ppp Z 4. aaa VU VU AC/VU AC AC

Mosaic analysis in C. elegans ncl-1+ lin-12+ ncl-1 q. Dp 3 lin-12 q. Dp 3 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

Mosaic analysis in C. elegans Individual A Z 1. ppp Individual B Z 4. aaa lin-12 AC VU + Z 1. ppp lin-12 VU Z 4. aaa + lin-12 AC

Mosaic analysis in C. elegans Individual A Z 1. ppp Individual B Z 4. aaa lin-12 AC VU + Z 1. ppp lin-12 VU Z 4. aaa + lin-12 AC Lin-12 activity is required in the VU cell