Types of lineage mutants

1
Lecture 10

• Types of lineage mutants
• Lateral inhibition in C. elegans
• Induction in C. elegans

2
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

3
Mutant names and origins
unc-93 (e1400)
allele
Complementation group
Phenotypic class ie screen isolated in
lin-22(n372)
4
Cell lineage mutants

• Canonical cell lineage
• Stem cell like mutant lineages
• Homeotic mutant lineages
• Heterochronic mutant lineages

5
Canonical cell lineage
Horvitz The Nematode C. elegans 1988
6
Canonical cell lineage
A
B
C
Horvitz The Nematode C. elegans 1988
7
Canonical cell mutant lineages
A
wild-type
B
C
A
A
B
A
B
B
8
Canonical cell mutant lineages
A
wild-type
B
C
Regeneration of the mother cell fate stem cell
like
A
A
B
A
B
B
9
Stem cell like mutant lineages
Horvitz The Nematode C. elegans 1988
10
Canonical cell mutant lineages
A
wild-type
B
C
Sisters have the same fate homeotic
A
A
B
A
B
B
11
Homeotic transformation
The transformation of one body part into the
likeness of another
12
Antennapedia can be misexpressed either by
spontaneous mutation or by genetic engineering.
Antp
ry
hsp
Antenna to second leg transformation
13
(No Transcript)
14
Canonical cell mutant lineages
A
wild-type
B
C
Sisters have the same fate homeotic
A
A
B
A
B
B
15
Cell lineage homeotic transformation
Horvitz The Nematode C. elegans 1988
16
Homeotic transformation of several lineages
Horvitz The Nematode C. elegans 1988
17
Heterochronic genes
Slack and Ruvkun Annu. Rev. Genet. 31, 611
18
Heterochronic genes
Slack and Ruvkun Annu. Rev. Genet. 31, 611
19
Heterochronic genes
Precious development of L2 lineage
Slack and Ruvkun Annu. Rev. Genet. 31, 611
20
Heterochronic genes
Suppression of L2 lineage and replacement with L1
lineage.
Slack and Ruvkun Annu. Rev. Genet. 31, 611
21
Heterochronic genes
wt
lin14lf
lin14gf
ON
ON
OFF
L1
lin-14 activity
ON
OFF
OFF
L2
22
Heterochronic genes
Slack and Ruvkun Annu. Rev. Genet. 31, 611
23
Heterochronic genes
Slack and Ruvkun Annu. Rev. Genet. 31, 611
24
Heterochronic genes
lin-14
lin-4
25
Heterochronic genes
lin-14 encodes a nuclear protein lin-4 encodes a
non-coding RNA a micro-RNA-the first found
26
Heterochronic genes
lin-4 RNA base pairs with the lin-14 3 UTR
In lin-14gf mutants the lin-4 binding sites are
deleted.
Slack and Ruvkun Annu. Rev. Genet. 31, 611
27
Heterochronic genes
lin-14 mRNA
Levels
L1
L2
L3
L4
28
Heterochronic genes
Levels
lin-14 protein
L1
L2
L3
L4
29
Heterochronic genes
lin-14 protein
Levels
lin-4 micRNA
L1
L2
L3
L4
30
Temporal Morphogen hypothesis
Kalthoff Analysis of Biological development 2nd ed
31
Lateral inhibition
Order arising from nothing an emergent property
Gilbert Developmental Biology 5th ed
32
Lateral inhibition
Order arising from nothing an emergent property
Gilbert Developmental Biology 5th ed
33
Anchor cell/ Ventral uterine cell equivalence
group
Individual A
Individual B
Z1.ppp
Z1.ppp
Z4.aaa
Z4.aaa
AC
AC
VU
VU
34
Model for AC/VU decision
Gilbert Developmental Biology 5th ed
35
Model for AC/VU decision
Equivalent signaling
Gilbert Developmental Biology 5th ed
36
Model for AC/VU decision
Stochastic difference in signaling
Gilbert Developmental Biology 5th ed
37
Model for AC/VU decision
Differential expression of receptor and ligand
Gilbert Developmental Biology 5th ed
38
Model for AC/VU decision
Determined cell fates
Gilbert Developmental Biology 5th ed
39
Genetic analysis of lateral inhibition
Z1.ppp
Z4.aaa
lin-12gf
VU
VU
AC/VU
AC/VU
lin-12(wt)
AC
AC
lin-12lf
40
Mosaic analysis in C. elegans
ncl-1
lin-12
qDp3
ncl-1
lin-12
qDp3 is a free duplication that is mitotically
unstable and is lost forming clones of ncl-1
lin-12 cells
41
Mosaic analysis in C. elegans
ncl-1
ncl-1
In ncl-1 cells, the nucleolus is large.
42
Mosaic analysis in C. elegans
ncl-1 lin-12 cell
Seydoux and Greenwald Cell 57, 1237
43
Mosaic analysis in C. elegans
Individual A
Individual B
Z1.ppp
Z1.ppp
Z4.aaa
Z4.aaa
lin-12
lin-12
lin-12
lin-12
AC
AC
VU
VU
44
Mosaic analysis in C. elegans
Individual A
Individual B
Z1.ppp
Z1.ppp
Z4.aaa
Z4.aaa
lin-12
lin-12
lin-12
lin-12
AC
AC
VU
VU
Lin-12 activity is required in the VU cell
45
Model for AC/VU decision
Gilbert Developmental Biology 5th ed
46
Expression of Lin-12 protein
Precommitment
Committed
Levitan and Greenwald Development 125, 3101
47
Induction of the vulva in C. elegans
48
Vulva equivalence group
Wormbase
49
Induction of the vulva in C. elegans
Horvitz and Sternberg Nature 351, 535
50
Induction of the vulva in C. elegans
Horvitz and Sternberg Nature 351, 535
51
Induction of the vulva in C. elegans
Horvitz and Sternberg Nature 351, 535
52
Induction of the vulva in C. elegans
Horvitz and Sternberg Nature 351, 535
53
Induction of the vulva in C. elegans
Horvitz and Sternberg Nature 351, 535
54
Induction of the vulva in C. elegans
Horvitz and Sternberg Nature 351, 535
55
Induction of the vulva in C. elegans
wild-type
Vulvaless Vul
Multivulva Muv
Ferguson and Horvitz Genetics 110, 17
56
Induction of the vulva in C. elegans
Ferguson et al. Nature 326, 259
57
Induction of the vulva in C. elegans
Wormbase
58
Lin-3 a morphogen?
At high concentration of Lin-3 1 fate At
medium concentration of Lin-3 2 fate At low
concentration of Lin-3 3 fate