A miR Image of Stem Cells and Their Lineages - Current Topics in Developmental Biology - page 181

of great interest to examine mammalian Dicer homologues share this func-
tion that is independent of the miR pathway, and if so, how it might be
differentially regulated in the epidermis and HF.
6. Conditional Ablation of Dgcr8
While studies with Dicer cKO skin provided a glimpse of how miRs
may be functioning in the skin, two key questions arise: (1) Are the
phenotypes observed in the Dicer cKO truly caused by depletion of mature
miRs? and (2) Are miRs the only Dicer products in the skin? To address
these questions, researchers engineered the equivalent K14-Cre -driven
cKO of Dgcr8 , thereby targeting an essential nuclear cofactor for miR
processing. Moreover, while Dicer has been reported to control the proces-
sing of both miRs- and mRNA-derived small RNAs ( Babiarz et al ., 2008;
Tam et al ., 2008; Watanabe et al ., 2008 ), Dgcr8 is specific for stereotypical
miRs ( Babiarz et al ., 2008; Yi et al ., 2009 ).
When comparing the number of deep sequencing reads that can be
mapped to different classes of small RNAs, stereotypical miRs emerged as
the most abundant species in the skin ( Yi et al ., 2009 ). In comparing the reads
between the K14-Cre X Dicer and K14-Cre X Dgcr8 cKO skins, the produc-
tion of the overwhelming majority of miRs was dependent upon both Dicer
and Dgcr8, while only a few hairpin miR- and mRNA-derived small RNAs
showed dependency only upon Dicer and not Dgcr8 ( Yi et al ., 2009 ).
Most importantly, both Dicer and Dgcr8 skin cKO animals displayed
indistinguishable phenotypes including evaginating HFs, enriched apoptosis
in hair bulbs, rough and dehydrated skin, and neonatal lethality. Thus, these
results confirmed that the previously reported Dicer cKO skin phenotypes
( Andl et al ., 2006; Yi et al ., 2006 ) were indeed bona fide consequences of the
loss of miRs in the skin and firmly established that stereotypical miRs are the
key Dicer products in skin.
7. Dissecting the Complexities of the
Differential Expression of miRs in Skin
By investigating Dicer and Dgcr8 skin cKOs, the global importance of
miRs in skin development was established and the differential effects on the
epidermis versus HF pointed to a physiological relevance to their differential
expression. With this information at hand, the next step was to begin to
unearth the functions of individual miRs in the skin.
miR-203 is highly expressed in a spatiotemporal-specific manner in
vertebrate epidermis ( Aberdam et al ., 2008; Lena et al ., 2008; Sonkoly